Objective This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1(PCED1B-AS1)in the development of hepatocellular carcinoma(HCC).Methods A total of 62 pairs of HCC tissues and adjacent non-t...Objective This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1(PCED1B-AS1)in the development of hepatocellular carcinoma(HCC).Methods A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients.The interactions of PCED1B-AS1 and microRNA-34a(miR-34a)were detected by dual luciferase activity assay and RNA pull-down assay.The RNA expression levels of PCED1B-AS1,miR-34a and CD44 were detected by RT-qPCR,and the protein expression level of CD44 was determined by Western blotting.The cell proliferation was detected by cell proliferation assay,and the cell invasion and migration by transwell invasion assay.The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study.Results PCED1B-AS1 was highly expressed in HCC tissues,which was associated with poor survival of HCC patients.Furthermore,PCED1B-AS1 interacted with miR-34a in HCC cells,but they did not regulate the expression of each other.Additionally,PCED1B-AS1 increased the expression level of CD44,which was targeted by miR-34a.The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro,while CD44 exhibited the opposite effects.Furthermore,PCED1B-AS1 suppressed the role of miR-34a.Moreover,the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo.Conclusion PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.展开更多
BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 p...BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.gdc.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://starbase.sysu.edu.cn/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with siRNA to knock down the expression of FTO,the expression levels of GATA6-AS1 were up-regulated.Finally,the proliferation,migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.CONCLUSION During the occurrence and development of gastric cancer,the overexpression of FTO may inhibit the expression of GATA6-AS1,thus promoting the proliferation and metastasis of gastric cancer.展开更多
BACKGROUND China's most frequent malignancy is gastric cancer(GC),which has a very poor survival rate,and the survival rate for patients with advanced GC is dismal.Pyroptosis has been connected to the genesis and ...BACKGROUND China's most frequent malignancy is gastric cancer(GC),which has a very poor survival rate,and the survival rate for patients with advanced GC is dismal.Pyroptosis has been connected to the genesis and development of cancer.The function of pyroptosis-related long non-coding RNAs(PRLs)in GC,on the other hand,remains uncertain.AIM To explore the construction and comprehensive analysis of the prognostic characteristics of long non-coding RNA(lncRNA)related to pyroptosis in GC patients.METHODS The TCGA database provided us with 352 stomach adenocarcinoma samples,and we obtained 28 pyroptotic genes from the Reactome database.We examined the correlation between lncRNAs and pyroptosis using the Pearson correlation coefficient.Prognosis-related PRLs were identified through univariate Cox analysis.A predictive signature was constructed using stepwise Cox regression analysis,and its reliability and independence were assessed.To facilitate clinical application,a nomogram was created based on this signature.we analyzed differences in immune cell infiltration,immune function,and checkpoints between the high-risk group(HRG)and low-risk group(LRG).RESULTS Five hundred and twenty-three PRLs were screened from all lncRNAs(absolute correlation coefficient>0.4,P<0.05).Nine PRLs were included in the risk prediction signature that was created through stepwise Cox regression analysis.We determined the risk score for GC patients and employed the median value as the dividing line between HRG and LRG.The ability of the risk signature to predict the overall survival(OS)of GC is demonstrated by the Kaplan-Meier analysis,risk curve,receiver operating characteristic curve,and decision curve analysis curve.The risk signature was shown to be an independent prognostic factor for OS in both univariate and multivariate Cox regression analyses.HRG showed a more efficient local immune response or modulation compared to LRG,as indicated by the predicted signal pathway analysis and examination of immune cell infiltration,function,and checkpoints(P<0.05).CONCLUSION In general,we have created a brand-new prognostic signature using PRLs,which may provide ideas for immunotherapy in patients with GC.展开更多
Pear fruit senescence under high-and low-temperature conditions has been reported to be mediated by microRNAs.Long non-coding RNAs(lncRNAs),which can function as competing endogenous RNAs that interact with microRNAs,...Pear fruit senescence under high-and low-temperature conditions has been reported to be mediated by microRNAs.Long non-coding RNAs(lncRNAs),which can function as competing endogenous RNAs that interact with microRNAs,may also be involved in temperature-affected fruit senescence.Based on the transcriptome and microRNA sequencings,in this study,3330 lncRNAs were isolated from Pyrus pyrifolia fruit.Of these lncRNAs,2060 and 537 were responsive to high-and low-temperature conditions,respectively.Of these differentially expressed lncRNAs,82 and 24 correlated to the mRNAs involved in fruit senescence under high-and low-temperature conditions,respectively.Moreover,three lncRNAs were predicted to be competing endogenous RNAs(ceRNAs)that interact with the microRNAs involved in fruit senescence,while one and two ceRNAs were involved in fruit senescence under high-and low-temperature conditions,respectively.A dual-luciferase assay showed that the interaction of an lncRNA with a microRNA disrupts the action of the microRNA on the expression of its target mRNA(s).Furthermore,four alternative splicing-derived lncRNAs interacted with miR172i homologies(Novel_88 and Novel_69)to relieve the repressed expression of their target and produce an miR172i precursor.Correlation analysis of microRNA expression suggested that Novel_69 is likely involved in the cleavage of the pre-miR172i hairpin to generate mature miR172i.Taken together,lncRNAs are involved in pear fruit senescence under high-or low-temperature conditions through ceRNAs and the production of microRNA.展开更多
Long non-coding RNAs(lncRNAs)regulate a variety of biological processes,including sexual reproduction and differentiation.Saccharina japonica,a commercially important brown alga in China,shows remarkable sexual dimorp...Long non-coding RNAs(lncRNAs)regulate a variety of biological processes,including sexual reproduction and differentiation.Saccharina japonica,a commercially important brown alga in China,shows remarkable sexual dimorphism in haploid gametophytes.The sex of Saccharina japonica gametophytes is determined by UV sexual system.However,no results have been reported on the lncRNAs involved in the sex-related gene regulation of S.japonica.This study identified a number of lncRNAs and assessed their expression levels in male and female gametophytes.Among them,a total of 405 lncRNAs and 211 mRNAs showed differential expressions.Furthermore,the functions of target genes of differentially expressed lncRNAs(DELs)differed from those of differentially expressed genes(DEGs),suggesting that lncRNA may interact with other functional proteins,in addition to DEGs,to involve sex regulation in S.japonica.There were 32 and 90 potential cis-regulatory and trans-regulatory interactions between DELsDEGs,respectively.Five of these lncRNAs(LNC_002974,LNC_021059,LNC_038466,LNC_051584,and LNC_027400)interacted with putative male sex determination region(SDR)genes,suggesting that they act as regulators in gametophytes'sex regulation potentially.Findings from this study contribute to our understanding of the roles of lncRNAs in sex differentiation and lay the foundation for functional studies of candidate lncRNAs in the future.展开更多
Long non-coding RNAs(lncRNAs)are a class of transcripts longer than 200 bp,which have been emerged as essential regulators in numerous biological processes.Black rockfish(Sebastes schlegelii)is an economic fish that w...Long non-coding RNAs(lncRNAs)are a class of transcripts longer than 200 bp,which have been emerged as essential regulators in numerous biological processes.Black rockfish(Sebastes schlegelii)is an economic fish that widely cultured in the coastal areas of China,Japan,and South Korea.With the expansion of aquacultural scale,various pathogens have threatened its industry and reduced its economic values.It has been reported that lncRNA were involved in the immune response and metabolic pathway in teleost,while no study is available on identification and functional analysis of lncRNAs in black rockfish so far.Herein,this study was performed to identify lncRNAs in the intestine of black rockfish after Edwardsiella tarda infection.In our results,a total of 9311 lncRNAs were identified through highthroughput sequencing,and 102 lncRNAs were significantly regulated following challenge,which were predicted to target 3348 mRNAs.Results of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the se target genes showed they were function in catalytic activity,hydrolase activity,defense response and peptidase activity,which involved in metabolic pathways and immune related pathways.In addition,47 lncRNAs and 8 differentially expressed mRNAs(DEmRNAs)showed co-expression at two or more infection time points with metabolism and immunity functions.Moreover,real-time quantitative PCR(qRT-PCR)was performed to verify the reliability of sequencing gene expression analysis results.This research laid the foundation for further investigation of the regulatory roles of lncRNAs in the intestinal immune response of black rockfish.展开更多
Background:Long non-coding RNAs(lncRNAs)play a vital role in autophagy modulation and tumor progression.However,the key lncRNAs and their functions in gastric cancer(GC)remain largely unknown.Methods:A bioinformatic a...Background:Long non-coding RNAs(lncRNAs)play a vital role in autophagy modulation and tumor progression.However,the key lncRNAs and their functions in gastric cancer(GC)remain largely unknown.Methods:A bioinformatic analysis of GC patients’gene expression profiling data from the Cancer Genome Atlas database was performed to identify autophagy-related lncRNAs that are associated with predictive risk.Through Cox regression and Lasso regression analyses,the autophagy-related lncRNAs that are associated with prognosis were identified,and a novel prognostic model for GC was established.The model was then used to evaluate the clinical features and predictive risk of individuals with GC.By using two datasets,GSE 62254(n=300)and GSE 15459(n=192),from Gene Expression Omnibus,its effectiveness was verified.Gene set enrichment analysis according to hallmark and Kyoto Encyclopedia of Genes and Genomes were used to determine the possible biological roles of these lncRNAs.Furthermore,the HOXD antisense growth-associated long non-coding RNA(HAGLR)mechanism in GC was discovered through in vitro and in vivo experiments.Results:Six lncRNAs associated with autophagy in GC were identified,and a new prognostic risk model based on these lncRNAs was established.The six-lncRNA signature was significantly associated with adverse clinicopathological features and found to be an independent GC prognostic factor.The model was proven to be effective and robust by GSE62254 and GSE15459.According to gene set enrichment analysis,the six lncRNAs appeared to be tightly linked to autophagy-related and cancer-related mechanisms.HAGLR was also found to promote tumor growth by enhancing autophagy signaling in GC.Conclusion:A novel prognostic model integrating HAGLR that can effectively evaluate and predict the prognostic risk of GC patients was established.The results indicated that HAGLR promotes gastric cancer progression by enhancing autophagy and is anticipated to be a potential new target for the treatment of gastric cancer.展开更多
Aging is linked to the deterioration of many physical and cognitive abilities and is the leading risk factor for Alzheimer’s disease. The growing aging population is a significant healthcare problem globally that res...Aging is linked to the deterioration of many physical and cognitive abilities and is the leading risk factor for Alzheimer’s disease. The growing aging population is a significant healthcare problem globally that researchers must investigate to better understand the underlying aging processes. Advances in microarrays and sequencing techniques have resulted in deeper analyses of diverse essential genomes(e.g., mouse, human, and rat) and their corresponding cell types, their organ-specific transcriptomes, and the tissue involved in aging. Traditional gene controllers such as DNA-and RNA-binding proteins significantly influence such programs, causing the need to sort out long non-coding RNAs, a new class of powerful gene regulatory elements. However, their functional significance in the aging process and senescence has yet to be investigated and identified. Several recent researchers have associated the initiation and development of senescence and aging in mammals with several well-reported and novel long non-coding RNAs. In this review article, we identified and analyzed the evolving functions of long non-coding RNAs in cellular processes, including cellular senescence, aging, and age-related pathogenesis, which are the major hallmarks of long non-coding RNAs in aging.展开更多
BACKGROUND Long non-coding RNA(lncRNA)is abnormally expressed in various malignant tumors.In recent years,it has been found that IncRNA HULC is increasingly expressed in pancreatic cancer tissues and is involved in th...BACKGROUND Long non-coding RNA(lncRNA)is abnormally expressed in various malignant tumors.In recent years,it has been found that IncRNA HULC is increasingly expressed in pancreatic cancer tissues and is involved in the development and progression of pancreatic cancer.However,the clinical value of serum HULC in pancreatic cancer remains unclear,and there are few studies on how HULC regulates the biological function of pancreatic cancer cells.AIM To determine the value of lncRNA HULC in the diagnosis and prognosis of pancreatic cancer,and its possible biological potential.METHODS Sixty patients with pancreatic cancer and sixty patients with benign pancreatic diseases admitted to Xiangya Hospital,Central South University were assigned to the pancreatic cancer group and the benign disease group,respectively,and another 60 healthy subjects were enrolled as the normal group during the same period.HULC-siRNA and NC-siRNA were transfected into pancreatic cancer cells.Quantitative real-time polymerase chain reaction was performed to determine the expression of HULC in tissues,serum,and cells.Western Blot was carried out to determine the expression ofβ-catenin,c-myc,and cyclin D1 in cells,and the cell counting kit-8,flow cytometry,and Transwell assay were conducted to determine the proliferation,apoptosis and invasion of cells.RESULTS Highly expressed in the tissues and serum of pancreatic cancer patients,HULC showed good clinical value in distinguishing between patients with pancreatic cancer,patients with benign pancreatic diseases and healthy subjects.HULC was related to pathological parameters including tumor size,T staging,M staging and vascular invasion,and the area-under-the-curve for evaluating these four expression of HULC had a significantly higher 3-year overall survival(OS)and 5-year OS than those with high expression.T staging,M staging,vascular invasion,and HULC were independent prognostic factors affecting the 3-year OS of patients with pancreatic cancer.Inhibition of HULC expression prevented the proliferation and invasion of pancreatic cancer cells,promoted apoptosis,and inhibited the expression of Wnt/β-catenin signaling pathway-related proteins,β-catenin,c-myc,and cyclin D1.The Wnt/β-catenin signaling pathway agonist(LiCl)restored proliferation,apoptosis,and invasion of pancreatic cancer cells with inhibited expression of HULC.CONCLUSION HULC is an effective marker for the diagnosis and prognosis of pancreatic cancer,which may affect the biological function of pancreatic cancer cells through the Wnt/β-catenin signaling pathway.展开更多
Summary: This study aimed to examine the effect of long non-coding RNA (LncRNA) MEG3 on the biological behaviors of renal cell carcinoma (RCC) cells 786-0 and the possible mechanism. MEG3 expression levels were d...Summary: This study aimed to examine the effect of long non-coding RNA (LncRNA) MEG3 on the biological behaviors of renal cell carcinoma (RCC) cells 786-0 and the possible mechanism. MEG3 expression levels were detected by RT-qPCR in Rmaor tissues and adjacent non-tumor tissues from 29 RCC patients and in RCC lines 786-0 and SN12 and human embryonic kidney cell line 293T. Plasmids GV144-MEG3 (MEG3 overexpression plasmid) and GV144 (control plasmid) were stably transfected into 786-0 cells by using lipofectamine 2000. Cell viabilities were determined by MTT, cell apoptosis rates by flow cytometry following PE Annexin V and 7AAD staining, apoptosis-related protein expressions by Western blotting, and Bcl-2 mRNA by RT-qPCR in the transfected cells. The results showed that MEG3 was evidently downregulated in RCC tissues (P〈0.05) and RCC cell lines (P〈0.05). The viabilities of 786-0 cells were decreased significantly after transfection with GV144-MEG3 for over 24 h (P〈0.05). Consistently, the apoptosis rate was significantly increased in 786-0 cells transfected with GV144-MEG3 for 48 h (P〈0.05). Furthermore, overexpression of MEG3 could reduce the expression of Bcl-2 and procaspase-9 proteins, enhance the expression of cleaved caspase-9 protein, and promote the release of cytochrome c protein to cytoplasm (P〈0.05). Additionally, Bcl-2 mRNA level was declined by MEG3 overexpression (P〈0.05). It was concluded that MEG3 induces the apoptosis of RCC cells possibly by activating the mitochondrial pathway.展开更多
Schwann cells play a critical role in peripheral nerve regeneration through dedifferentiation and proliferation. In a previous study, we performed microarray analysis of the sciatic nerve after injury. Accordingly, we...Schwann cells play a critical role in peripheral nerve regeneration through dedifferentiation and proliferation. In a previous study, we performed microarray analysis of the sciatic nerve after injury. Accordingly, we predicted that long non-coding RNA NONMMUG014387 may promote Schwann cell proliferation after peripheral nerve injury, as bioinformatic analysis revealed that the target gene of NONMMUG014387 was collagen triple helix repeat containing 1(Cthrc1). Cthrc1 may promote cell proliferation in a variety of cells by activating Wnt/PCP signaling. Nonetheless, bioinformatic analysis still needs to be verified by biological experiment. In this study, the candidate long non-coding RNA, NONMMUG014387, was overexpressed in mouse Schwann cells by recombinant adenovirus transfection. Plasmid p HBAd-MCMV-GFP-NONMMUG014387 and p HBAd-MCMV-GFP were transfected into Schwann cells. Schwann cells were divided into three groups: control(Schwann cells without intervention), Ad-GFP(Schwann cells with GFP overexpression), and Ad-NONMMUGO148387(Schwann cells with GFP and NONMMUGO148387 overexpression). Cell Counting Kit-8 assay was used to evaluate proliferative capability of mouse Schwann cells after NONMMUG014387 overexpression. Polymerase chain reaction and western blot assay were performed to investigate target genes and downstream pathways of NONMMUG014387. Cell proliferation was significantly increased in Schwann cells overexpressing lnc RNA NONMMUG014387 compared with the other two groups. Further, compared with the control group, m RNA and protein levels of Cthrc1, Wnt5 a, ROR2, Rho A, Rac1, JNK, and ROCK were visibly up-regulated in the Ad-NONMMUGO148387 group. Our findings confirm that long non-coding RNA NONMMUG014387 can promote proliferation of Schwann cells surrounding the injury site through targeting Cthrc1 and activating the Wnt/PCP pathway.展开更多
Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular m...Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular mechanisms of lncRNAs in spinal cord injury(SCI),the expression signatures of lncRNAs were profiled using RNA sequencing(RNA-seq)technology in a Sprague-Dawley rat model of the 10th thoracic vertebra complete transection SCI.Results showed that 116 of 14,802 detected lncRNAs were differentially expressed,among which 16—including eight up-regulated(H19,Vof16,Hmox2-ps1,LOC100910973,Ybx1-ps3,Nnat,Gcgr,LOC680254)and eight down-regulated(Rmrp,Terc,Ngrn,Ppp2r2b,Cox6a2,Rpl37a-ps1,LOC360231,Rpph1)—demonstrated fold changes>2 in response to transection SCI.A subset of these RNA-seq results was validated by quantitative real-time PCR.The levels of 821 mRNAs were also significantly altered post-SCI;592 mRNAs were up-regulated and 229 mRNAs were down-regulated by more than 2-fold.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses showed that differentially expressed mRNAs were related to GO biological processes and molecular functions such as injury and inflammation response,wound repair,and apoptosis,and were significantly enriched in 15 KEGG pathways,including cell phagocytosis,tumor necrosis factor alpha pathway,and leukocyte migration.Our results reveal the expression profiles of lncRNAs and mRNAs in the rat spinal cord of a complete transection model,and these differentially expressed lncRNAs and mRNAs represent potential novel targets for SCI treatment.We suggest that lncRNAs may play an important role in the early immuno-inflammatory response after spinal cord injury.This study was approved by the Administration Committee of Experimental Animals,Guangdong Province,China.展开更多
Whether long non-coding RNA myocardial infarction-associated transcript is involved in oxygen-induced retinopathy remains poorly understood. To validate this hypothesis, we established a newborn mouse model of oxygen-...Whether long non-coding RNA myocardial infarction-associated transcript is involved in oxygen-induced retinopathy remains poorly understood. To validate this hypothesis, we established a newborn mouse model of oxygen-induced retinopathy by feeding in an oxygen concentration of 75 ± 2% from postnatal day 8 to postnatal day 12, followed by in normal air. On postnatal day 11, the mice were injected with the myocardial infarction-associated transcript siRNA plasmid via the vitreous cavity to knockdown long non-coding RNA myocardial infarction-associated transcript. Myocardial infarction-associated transcript siRNA transcription significantly inhibited myocardial infarctionassociated transcript mRNA expression, reduced the phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor immunopositivities, protein and mRNA expression, and alleviated the pathological damage to the retina of oxygen-induced retinopathy mouse models. These findings suggest that myocardial infarction-associated transcript is likely involved in the retinal neovascularization in retinopathy of prematurity and that inhibition of myocardial infarction-associated transcript can downregulate phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor expression levels and inhibit neovascularization. This study was approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University, China(approval No. 2016 PS074 K) on February 25, 2016.展开更多
In China, hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC), which is called HBV-related HCC (HBV-HCC), but the pathogenesis has not been clearly elu- cidated. Long non-codin...In China, hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC), which is called HBV-related HCC (HBV-HCC), but the pathogenesis has not been clearly elu- cidated. Long non-coding RNAs (lncRNAs) have been paid increasing attention to, as an important regulatory molecule involved in many biological processes, as well as a variety of diseases. This study examined lncRNA that might play an important role in HBV-HCC pathogenesis by conducting lncRNA and mRNA profile comparison between HBV-HCC and normal liver tissues. The differentially ex- pressed lncRNA and mRNA profiles between HBV-HCC and normal liver tissues were analyzed by mi- croarrays. The potential protein-encoding gene regulated by lncRNA, and the biological function (gene ontology, pathway analysis) of the target gene were investigated. The results showed that the expression levels of lncRNA and mRNA in HBV-HCC tissues were different from those in normal liver tissues. As compared with normal liver tissue, 837 (4.30%) lncRNAs exhibited more than two-fold change (P〈0.05); 325 were up-regulated, and 512 were down-regulated; 991 (5.70%) mRNAs exhibited more than 2-fold change (P〈0.05); 733 were up-regulated and 258 were down-regulated in HBV-HCC tissue. Besides, there were 7 lncRNAs with above 10-fold elevation, 6 lncRNAs with above 10-fold decrease, 18 mRNAs with above 10-fold elevation and 11 mRNAs with above 10-fold decrease. 444 (53.05%) lncRNAs had their corresponding mRNAs, some of which were adjacent to lncRNAs. The biological analysis showed that the target gene of differentially expressed lncRNAs took part in the important bio- logical regulatory function. Target gene-related pathway analysis revealed the pathways in carcinoma and mitogen-activated protein kinase (MAPK) signaling pathways significantly changed in the HBV-HCC tissues as compared with normal liver tissues (P〈0.05). It was suggested that as compared with normal liver tissues, the expression of lncRNAs in HBV-HCC tissues changed significantly, and lncRNAs played a key role in the pathogenesis of HBV-HCC probably by mainly regulating the carci- noma-related signaling pathway and MAPK signaling pathways.展开更多
Severe cerebral ischemia/reperfusion injury has been shown to induce high-level autophagy and neuronal death.Therefore,it is extremely important to search for a target that inhibits autophagy activation.Long non-codin...Severe cerebral ischemia/reperfusion injury has been shown to induce high-level autophagy and neuronal death.Therefore,it is extremely important to search for a target that inhibits autophagy activation.Long non-coding RNA MEG3 participates in autophagy.However,it remains unclear whether it can be targeted to regulate cerebral ischemia/reperfusion injury.Our results revealed that in oxygen and glucose deprivation/reoxygenation-treated HT22 cells,MEG3 expression was obviously upregulated,and autophagy was increased,while knockdown of MEG3 expression greatly reduced autophagy.Furthermore,MEG3 bound mi R-181 c-5 p and inhibited its expression,while mi R-181 c-5 p bound to autophagy-related gene ATG7 and inhibited its expression.Further experiments revealed that mir-181 c-5 p overexpression reversed the effect of MEG3 on autophagy and ATG7 expression in HT22 cells subjected to oxygen and glucose deprivation/reoxygenation.In vivo experiments revealed that MEG3 knockdown suppressed autophagy,infarct volume and behavioral deficits in cerebral ischemia/reperfusion mice.These findings suggest that MEG3 knockdown inhibited autophagy and alleviated cerebral ischemia/reperfusion injury through the mi R-181 c-5 p/ATG7 signaling pathway.Therefore,MEG3 can be considered as an intervention target for the treatment of cerebral ischemia/reperfusion injury.This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Zhengzhou University,China(approval No.XF20190538)on January 4,2019.展开更多
Long non-coding RNAs(lncRNAs) play important roles in response to various biotic and abiotic stresses. So far, systematic identification and characterization of lncRNAs have been reported in a few model plant species ...Long non-coding RNAs(lncRNAs) play important roles in response to various biotic and abiotic stresses. So far, systematic identification and characterization of lncRNAs have been reported in a few model plant species and major crops, but their roles in abiotic stress response have not yet been reported in common wild rice(Oryza rufipogon). Dongxiang wild rice(DXWR) possesses a high degree of drought resistance and has been well recognized as a precious genetic resource for drought resistant rice breeding. We presented the reference catalog of 1 655 novel lncRNA transcripts in DXWR using strand-specific RNA sequencing and bioinformatics approaches. Meanwhile, a total of 1092 lncRNAs were determined as differentially expressed lncRNAs under drought stress. Quantitative real-time PCR results exhibited a high concordance with RNA sequencing data, which confirmed that the expression patterns of lncRNAs based on RNA sequencing were highly reliable. Furthermore, 8 711 transcripts were predicted as target genes of the differentially expressed lncRNAs. Functional annotation analysis based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases showed that the target genes were significantly enriched in cellular and metabolic processes, cell part, binding and plant hormone signal transduction, as well as many other terms related to abiotic stress resistance. These results expanded our understanding of lncRNA biology and provided candidate regulators for genetic improvement of drought resistance in rice cultivars.展开更多
BACKGROUND Long non-coding RNAs(lncRNAs) have been shown to be associated with many tumors. However, the specific mechanism of lncRNAs in the occurrence and development of gastric cancer(GC) has not been fully elucida...BACKGROUND Long non-coding RNAs(lncRNAs) have been shown to be associated with many tumors. However, the specific mechanism of lncRNAs in the occurrence and development of gastric cancer(GC) has not been fully elucidated.AIM To explore the expression level and molecular mechanism of HOXD-AS2 in GC tissues and cells, and analyze its significance in the prognosis of GC.METHODS Real-time quantitative PCR was used to detect the expression of HOXD-AS2 in 79 pairs of GC tissues and five cell lines. The pc HOXD-AS2 plasmid vector was constructed and transfected into SGC-7901 and SNU-1 GC cells. Matrigel Transwell and wound healing assays were used to confirm the effect of HOXDAS2 on invasion and migration of GC cells. Cell counting kit-8 assay and flow cytometry were used to verify the effect of HOXD-AS2 on the proliferation, cell cycle, and apoptosis of GC cells. The relevant regulatory mechanism between HOXD-AS2 and HOXD8 and PI3K/Akt signaling pathway was verified by Western blot analysis.RESULTS The low expression of lncRNA HOXD-AS2 was associated with lymph node metastasis and tumor-node-metastasis stage in GC. In vitro functional experiments demonstrated that overexpression of HOXD-AS2 inhibited GC cell progression. Mechanistic studies revealed that HOXD-AS2 regulated the expression of its nearby gene HOXD8 and inhibited the activity of the PI3K/Akt signaling pathway.CONCLUSION These results indicate that downregulation of HOXD-AS2 significantly promotes the progression of GC cells by regulating HOXD8 expression and activating the PI3K/Akt signaling pathway. HOXD-AS2 may be a novel diagnostic biomarker and effective therapeutic target for GC.展开更多
Long non-coding RNAs(lnc RNAs) are a subgroup of non-coding RNA transcripts greater than 200 nucleotides in length with little or no protein-coding potential. Emerging evidence indicates that lnc RNAs may play importa...Long non-coding RNAs(lnc RNAs) are a subgroup of non-coding RNA transcripts greater than 200 nucleotides in length with little or no protein-coding potential. Emerging evidence indicates that lnc RNAs may play important regulatory roles in the pathogenesis and progression of human cancers, including hepatocellular carcinoma(HCC). Certain lnc RNAs may be used as diagnostic or prognostic markers for HCC, a serious malignancy with increasing morbidity and high mortality rates worldwide. Therefore, elucidating the functional roles of lnc RNAs in tumors can contribute to a better understanding of the molecular mechanisms of HCC and may help in developing novel therapeutic targets. In this review, we summarize the recent progress regarding the functional roles of lnc RNAs in HCC and explore their clinical implications as diagnostic or prognostic biomarkers and molecular therapeutic targets for HCC.展开更多
Background:Hepatectomy and liver transplantation(LT)are the two most commonly performed surgical procedures for various hepatic lesions.micro RNA(mi RNA)and long non-coding RNA(lnc RNA)have been gradually unveiled the...Background:Hepatectomy and liver transplantation(LT)are the two most commonly performed surgical procedures for various hepatic lesions.micro RNA(mi RNA)and long non-coding RNA(lnc RNA)have been gradually unveiled their roles as either biomarkers for early diagnosis or potentially therapeutic tools to manipulate gene expression in many disease entities.This review aimed to discuss the effects of mi RNA or lnc RNA in the hepatectomy and LT fields.Data sources:We did a literature search from 1990 through January 2018 to summarize the currently available evidence with respect to the effects of mi RNA and lnc RNA in liver regeneration after partial hepatectomy,as well as their involvement in several key issues related to LT,including ischemia-reperfusion injury,allograft rejection,tolerance,recurrence of original hepatic malignancies,etc.Results:Certain mi RNAs and lnc RNAs are actively involved in the regulation of various aspects of liver resection and transplantation.During the process of liver regeneration after hepatectomy,the expression of mi RNAs and lnc RNAs shows dynamic changes.Conclusions:It is now clear that mi RNAs and lnc RNAs orchestrate in various aspects of the pathophysiological process of LT and hepatectomy.Better understanding of the underlying mechanism and future clinical trials may strengthen their positions as either biomarkers or potential therapeutic targets in the management of complications after liver surgery.展开更多
Objective To explore novel long non-coding RNA(lncRNA)molecular markers related to bladder cancer prognosis and to construct a prognostic prediction model for bladder cancer patients.Methods LncRNA expression data of ...Objective To explore novel long non-coding RNA(lncRNA)molecular markers related to bladder cancer prognosis and to construct a prognostic prediction model for bladder cancer patients.Methods LncRNA expression data of patients with bladder cancer were downloaded from TCGA database.Univariate Cox regression and likelihood-based survival analysis were used to discover prognosis related lncRNAs.Functional studies of prognosis related lncRNAs were conducted by co-expression analysis and pathway enrichment analysis.Multivariate Cox regression analysis was used to establish risk score model,and Receiver Operating Characteristic analysis was used to determine the optimal cut-off point of the model.The risk score model was validated through Kaplan Meier estimation method and log-rank test.Results Seven prognosis related lncRNAs(OCIAD1-AS1,RP11-111 J6.2,AC079354.3,RP11-553 A21.3,RP11-598 F7.3,CYP4 F35 P and RP11-113 K21.4)which can predict survival of bladder cancer patient were discovered.Co-expression analysis and pathway analysis of these novel lncRNA signature and their target genes further revealed that these lncRNAs play important roles in the occurrence and development of bladder cancer.Additionally,a seven-lncRNA signature based risk score model for prognostic prediction of bladder cancer patients was established and validated.Notably,we identified the potential significance of two tumor-related antisense lncRNAs(OCIAD1-AS1 and RP11-553 A21.3)in the prognosis of bladder cancer.Conclusion Our results suggest that these lncRNA markers may serve as potential prognosis predictors for bladder cancer and deserve further functional verification studies.展开更多
基金supported by the Medical Science and Technology Research Foundation of Guangdong Province(No.A2020559).
文摘Objective This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1(PCED1B-AS1)in the development of hepatocellular carcinoma(HCC).Methods A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients.The interactions of PCED1B-AS1 and microRNA-34a(miR-34a)were detected by dual luciferase activity assay and RNA pull-down assay.The RNA expression levels of PCED1B-AS1,miR-34a and CD44 were detected by RT-qPCR,and the protein expression level of CD44 was determined by Western blotting.The cell proliferation was detected by cell proliferation assay,and the cell invasion and migration by transwell invasion assay.The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study.Results PCED1B-AS1 was highly expressed in HCC tissues,which was associated with poor survival of HCC patients.Furthermore,PCED1B-AS1 interacted with miR-34a in HCC cells,but they did not regulate the expression of each other.Additionally,PCED1B-AS1 increased the expression level of CD44,which was targeted by miR-34a.The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro,while CD44 exhibited the opposite effects.Furthermore,PCED1B-AS1 suppressed the role of miR-34a.Moreover,the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo.Conclusion PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.
基金Natural Science Foundation of Shandong Province,No.ZR2020MH207 and No.ZR2020MH251.
文摘BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.gdc.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://starbase.sysu.edu.cn/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with siRNA to knock down the expression of FTO,the expression levels of GATA6-AS1 were up-regulated.Finally,the proliferation,migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.CONCLUSION During the occurrence and development of gastric cancer,the overexpression of FTO may inhibit the expression of GATA6-AS1,thus promoting the proliferation and metastasis of gastric cancer.
基金Supported by The Scientific Research Project of Integrated Traditional Chinese and Western Medicine of Tianjin Health Commission Administration of Traditional Chinese Medicine,No.2021010 and No.2023166Xiao-Ping Chen Foundation for the Development of Science and Technology of Hubei Province,No.CXPJJH122002-073.
文摘BACKGROUND China's most frequent malignancy is gastric cancer(GC),which has a very poor survival rate,and the survival rate for patients with advanced GC is dismal.Pyroptosis has been connected to the genesis and development of cancer.The function of pyroptosis-related long non-coding RNAs(PRLs)in GC,on the other hand,remains uncertain.AIM To explore the construction and comprehensive analysis of the prognostic characteristics of long non-coding RNA(lncRNA)related to pyroptosis in GC patients.METHODS The TCGA database provided us with 352 stomach adenocarcinoma samples,and we obtained 28 pyroptotic genes from the Reactome database.We examined the correlation between lncRNAs and pyroptosis using the Pearson correlation coefficient.Prognosis-related PRLs were identified through univariate Cox analysis.A predictive signature was constructed using stepwise Cox regression analysis,and its reliability and independence were assessed.To facilitate clinical application,a nomogram was created based on this signature.we analyzed differences in immune cell infiltration,immune function,and checkpoints between the high-risk group(HRG)and low-risk group(LRG).RESULTS Five hundred and twenty-three PRLs were screened from all lncRNAs(absolute correlation coefficient>0.4,P<0.05).Nine PRLs were included in the risk prediction signature that was created through stepwise Cox regression analysis.We determined the risk score for GC patients and employed the median value as the dividing line between HRG and LRG.The ability of the risk signature to predict the overall survival(OS)of GC is demonstrated by the Kaplan-Meier analysis,risk curve,receiver operating characteristic curve,and decision curve analysis curve.The risk signature was shown to be an independent prognostic factor for OS in both univariate and multivariate Cox regression analyses.HRG showed a more efficient local immune response or modulation compared to LRG,as indicated by the predicted signal pathway analysis and examination of immune cell infiltration,function,and checkpoints(P<0.05).CONCLUSION In general,we have created a brand-new prognostic signature using PRLs,which may provide ideas for immunotherapy in patients with GC.
基金supported by the Fundamental Research Funds for the Central Universities(Grant No.KYYJ202116)the Jiangsu Agricultural Science and Technology Innovation Fund[Grant No.CX(20)2020]the Earmarked Fund for China Agriculture Research System(Grant No.CARS-28).
文摘Pear fruit senescence under high-and low-temperature conditions has been reported to be mediated by microRNAs.Long non-coding RNAs(lncRNAs),which can function as competing endogenous RNAs that interact with microRNAs,may also be involved in temperature-affected fruit senescence.Based on the transcriptome and microRNA sequencings,in this study,3330 lncRNAs were isolated from Pyrus pyrifolia fruit.Of these lncRNAs,2060 and 537 were responsive to high-and low-temperature conditions,respectively.Of these differentially expressed lncRNAs,82 and 24 correlated to the mRNAs involved in fruit senescence under high-and low-temperature conditions,respectively.Moreover,three lncRNAs were predicted to be competing endogenous RNAs(ceRNAs)that interact with the microRNAs involved in fruit senescence,while one and two ceRNAs were involved in fruit senescence under high-and low-temperature conditions,respectively.A dual-luciferase assay showed that the interaction of an lncRNA with a microRNA disrupts the action of the microRNA on the expression of its target mRNA(s).Furthermore,four alternative splicing-derived lncRNAs interacted with miR172i homologies(Novel_88 and Novel_69)to relieve the repressed expression of their target and produce an miR172i precursor.Correlation analysis of microRNA expression suggested that Novel_69 is likely involved in the cleavage of the pre-miR172i hairpin to generate mature miR172i.Taken together,lncRNAs are involved in pear fruit senescence under high-or low-temperature conditions through ceRNAs and the production of microRNA.
基金supported by the National Natural Science Foundation of China(No.132072962)the Agricultural Industrial Technology System in Shandong Province(No.SDAIT-26)+3 种基金the‘First Class Fishery Discipline’Programme[(2020)3]in Shandong Provincethe Special Talent Programme‘Yishi Yiyi’in Shandong Province,Chinathe National Key R&D Program of China(No.2018YFD0901500)the Shandong Province Agriculture Seed Project(No.2021LZ GC004)。
文摘Long non-coding RNAs(lncRNAs)regulate a variety of biological processes,including sexual reproduction and differentiation.Saccharina japonica,a commercially important brown alga in China,shows remarkable sexual dimorphism in haploid gametophytes.The sex of Saccharina japonica gametophytes is determined by UV sexual system.However,no results have been reported on the lncRNAs involved in the sex-related gene regulation of S.japonica.This study identified a number of lncRNAs and assessed their expression levels in male and female gametophytes.Among them,a total of 405 lncRNAs and 211 mRNAs showed differential expressions.Furthermore,the functions of target genes of differentially expressed lncRNAs(DELs)differed from those of differentially expressed genes(DEGs),suggesting that lncRNA may interact with other functional proteins,in addition to DEGs,to involve sex regulation in S.japonica.There were 32 and 90 potential cis-regulatory and trans-regulatory interactions between DELsDEGs,respectively.Five of these lncRNAs(LNC_002974,LNC_021059,LNC_038466,LNC_051584,and LNC_027400)interacted with putative male sex determination region(SDR)genes,suggesting that they act as regulators in gametophytes'sex regulation potentially.Findings from this study contribute to our understanding of the roles of lncRNAs in sex differentiation and lay the foundation for functional studies of candidate lncRNAs in the future.
基金Supported by the Young Experts of Taishan Scholars(No.tsqn201909130)the Science and Technology Support Plan for Youth Innovation of Colleges and Universities in Shandong Province(No.2019KJF003)+1 种基金the“First Class Fishery Discipline”Program in Shandong Province,a special talent program“One Matter One Decision(Yi Shi Yi Yi)”Program in Shandong Province,Chinathe Breeding Plan of Shandong Provincial Qingchuang Research Team(2019)。
文摘Long non-coding RNAs(lncRNAs)are a class of transcripts longer than 200 bp,which have been emerged as essential regulators in numerous biological processes.Black rockfish(Sebastes schlegelii)is an economic fish that widely cultured in the coastal areas of China,Japan,and South Korea.With the expansion of aquacultural scale,various pathogens have threatened its industry and reduced its economic values.It has been reported that lncRNA were involved in the immune response and metabolic pathway in teleost,while no study is available on identification and functional analysis of lncRNAs in black rockfish so far.Herein,this study was performed to identify lncRNAs in the intestine of black rockfish after Edwardsiella tarda infection.In our results,a total of 9311 lncRNAs were identified through highthroughput sequencing,and 102 lncRNAs were significantly regulated following challenge,which were predicted to target 3348 mRNAs.Results of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the se target genes showed they were function in catalytic activity,hydrolase activity,defense response and peptidase activity,which involved in metabolic pathways and immune related pathways.In addition,47 lncRNAs and 8 differentially expressed mRNAs(DEmRNAs)showed co-expression at two or more infection time points with metabolism and immunity functions.Moreover,real-time quantitative PCR(qRT-PCR)was performed to verify the reliability of sequencing gene expression analysis results.This research laid the foundation for further investigation of the regulatory roles of lncRNAs in the intestinal immune response of black rockfish.
基金This study was funded by the Natural Science Foundation of Shanghai of China(No.20ZR1452300)National Natural Science Foundation of China(No.81874201)+1 种基金Shanghai Municipal Health Commission Foundation(No.201840359)Natural Science Foundation of Shanghai(No.20ZR1452500).
文摘Background:Long non-coding RNAs(lncRNAs)play a vital role in autophagy modulation and tumor progression.However,the key lncRNAs and their functions in gastric cancer(GC)remain largely unknown.Methods:A bioinformatic analysis of GC patients’gene expression profiling data from the Cancer Genome Atlas database was performed to identify autophagy-related lncRNAs that are associated with predictive risk.Through Cox regression and Lasso regression analyses,the autophagy-related lncRNAs that are associated with prognosis were identified,and a novel prognostic model for GC was established.The model was then used to evaluate the clinical features and predictive risk of individuals with GC.By using two datasets,GSE 62254(n=300)and GSE 15459(n=192),from Gene Expression Omnibus,its effectiveness was verified.Gene set enrichment analysis according to hallmark and Kyoto Encyclopedia of Genes and Genomes were used to determine the possible biological roles of these lncRNAs.Furthermore,the HOXD antisense growth-associated long non-coding RNA(HAGLR)mechanism in GC was discovered through in vitro and in vivo experiments.Results:Six lncRNAs associated with autophagy in GC were identified,and a new prognostic risk model based on these lncRNAs was established.The six-lncRNA signature was significantly associated with adverse clinicopathological features and found to be an independent GC prognostic factor.The model was proven to be effective and robust by GSE62254 and GSE15459.According to gene set enrichment analysis,the six lncRNAs appeared to be tightly linked to autophagy-related and cancer-related mechanisms.HAGLR was also found to promote tumor growth by enhancing autophagy signaling in GC.Conclusion:A novel prognostic model integrating HAGLR that can effectively evaluate and predict the prognostic risk of GC patients was established.The results indicated that HAGLR promotes gastric cancer progression by enhancing autophagy and is anticipated to be a potential new target for the treatment of gastric cancer.
文摘Aging is linked to the deterioration of many physical and cognitive abilities and is the leading risk factor for Alzheimer’s disease. The growing aging population is a significant healthcare problem globally that researchers must investigate to better understand the underlying aging processes. Advances in microarrays and sequencing techniques have resulted in deeper analyses of diverse essential genomes(e.g., mouse, human, and rat) and their corresponding cell types, their organ-specific transcriptomes, and the tissue involved in aging. Traditional gene controllers such as DNA-and RNA-binding proteins significantly influence such programs, causing the need to sort out long non-coding RNAs, a new class of powerful gene regulatory elements. However, their functional significance in the aging process and senescence has yet to be investigated and identified. Several recent researchers have associated the initiation and development of senescence and aging in mammals with several well-reported and novel long non-coding RNAs. In this review article, we identified and analyzed the evolving functions of long non-coding RNAs in cellular processes, including cellular senescence, aging, and age-related pathogenesis, which are the major hallmarks of long non-coding RNAs in aging.
基金Supported by the Hunan Natural Science Youth Foundation,No.2017JJ3508
文摘BACKGROUND Long non-coding RNA(lncRNA)is abnormally expressed in various malignant tumors.In recent years,it has been found that IncRNA HULC is increasingly expressed in pancreatic cancer tissues and is involved in the development and progression of pancreatic cancer.However,the clinical value of serum HULC in pancreatic cancer remains unclear,and there are few studies on how HULC regulates the biological function of pancreatic cancer cells.AIM To determine the value of lncRNA HULC in the diagnosis and prognosis of pancreatic cancer,and its possible biological potential.METHODS Sixty patients with pancreatic cancer and sixty patients with benign pancreatic diseases admitted to Xiangya Hospital,Central South University were assigned to the pancreatic cancer group and the benign disease group,respectively,and another 60 healthy subjects were enrolled as the normal group during the same period.HULC-siRNA and NC-siRNA were transfected into pancreatic cancer cells.Quantitative real-time polymerase chain reaction was performed to determine the expression of HULC in tissues,serum,and cells.Western Blot was carried out to determine the expression ofβ-catenin,c-myc,and cyclin D1 in cells,and the cell counting kit-8,flow cytometry,and Transwell assay were conducted to determine the proliferation,apoptosis and invasion of cells.RESULTS Highly expressed in the tissues and serum of pancreatic cancer patients,HULC showed good clinical value in distinguishing between patients with pancreatic cancer,patients with benign pancreatic diseases and healthy subjects.HULC was related to pathological parameters including tumor size,T staging,M staging and vascular invasion,and the area-under-the-curve for evaluating these four expression of HULC had a significantly higher 3-year overall survival(OS)and 5-year OS than those with high expression.T staging,M staging,vascular invasion,and HULC were independent prognostic factors affecting the 3-year OS of patients with pancreatic cancer.Inhibition of HULC expression prevented the proliferation and invasion of pancreatic cancer cells,promoted apoptosis,and inhibited the expression of Wnt/β-catenin signaling pathway-related proteins,β-catenin,c-myc,and cyclin D1.The Wnt/β-catenin signaling pathway agonist(LiCl)restored proliferation,apoptosis,and invasion of pancreatic cancer cells with inhibited expression of HULC.CONCLUSION HULC is an effective marker for the diagnosis and prognosis of pancreatic cancer,which may affect the biological function of pancreatic cancer cells through the Wnt/β-catenin signaling pathway.
基金supported by grants from the National Natural Science Foundation of China(Nos.81001132,81172423,and 81272816)
文摘Summary: This study aimed to examine the effect of long non-coding RNA (LncRNA) MEG3 on the biological behaviors of renal cell carcinoma (RCC) cells 786-0 and the possible mechanism. MEG3 expression levels were detected by RT-qPCR in Rmaor tissues and adjacent non-tumor tissues from 29 RCC patients and in RCC lines 786-0 and SN12 and human embryonic kidney cell line 293T. Plasmids GV144-MEG3 (MEG3 overexpression plasmid) and GV144 (control plasmid) were stably transfected into 786-0 cells by using lipofectamine 2000. Cell viabilities were determined by MTT, cell apoptosis rates by flow cytometry following PE Annexin V and 7AAD staining, apoptosis-related protein expressions by Western blotting, and Bcl-2 mRNA by RT-qPCR in the transfected cells. The results showed that MEG3 was evidently downregulated in RCC tissues (P〈0.05) and RCC cell lines (P〈0.05). The viabilities of 786-0 cells were decreased significantly after transfection with GV144-MEG3 for over 24 h (P〈0.05). Consistently, the apoptosis rate was significantly increased in 786-0 cells transfected with GV144-MEG3 for 48 h (P〈0.05). Furthermore, overexpression of MEG3 could reduce the expression of Bcl-2 and procaspase-9 proteins, enhance the expression of cleaved caspase-9 protein, and promote the release of cytochrome c protein to cytoplasm (P〈0.05). Additionally, Bcl-2 mRNA level was declined by MEG3 overexpression (P〈0.05). It was concluded that MEG3 induces the apoptosis of RCC cells possibly by activating the mitochondrial pathway.
基金supported by a grant from Student’s Platform for Innovation and Entrepreneurship Training Program in China,No.201610062009the National Natural Science Foundation of China(Key Program),No.81330042+1 种基金a grant from the Special Program for Sino-Russian Joint Research Sponsored by the Ministry of Science and Technology,China,No.2014DFR31210a grant from the Key Program Sponsored by the Tianjin Science and Technology Committee of China,No.13RCGFSY19000,14ZCZDSY00044
文摘Schwann cells play a critical role in peripheral nerve regeneration through dedifferentiation and proliferation. In a previous study, we performed microarray analysis of the sciatic nerve after injury. Accordingly, we predicted that long non-coding RNA NONMMUG014387 may promote Schwann cell proliferation after peripheral nerve injury, as bioinformatic analysis revealed that the target gene of NONMMUG014387 was collagen triple helix repeat containing 1(Cthrc1). Cthrc1 may promote cell proliferation in a variety of cells by activating Wnt/PCP signaling. Nonetheless, bioinformatic analysis still needs to be verified by biological experiment. In this study, the candidate long non-coding RNA, NONMMUG014387, was overexpressed in mouse Schwann cells by recombinant adenovirus transfection. Plasmid p HBAd-MCMV-GFP-NONMMUG014387 and p HBAd-MCMV-GFP were transfected into Schwann cells. Schwann cells were divided into three groups: control(Schwann cells without intervention), Ad-GFP(Schwann cells with GFP overexpression), and Ad-NONMMUGO148387(Schwann cells with GFP and NONMMUGO148387 overexpression). Cell Counting Kit-8 assay was used to evaluate proliferative capability of mouse Schwann cells after NONMMUG014387 overexpression. Polymerase chain reaction and western blot assay were performed to investigate target genes and downstream pathways of NONMMUG014387. Cell proliferation was significantly increased in Schwann cells overexpressing lnc RNA NONMMUG014387 compared with the other two groups. Further, compared with the control group, m RNA and protein levels of Cthrc1, Wnt5 a, ROR2, Rho A, Rac1, JNK, and ROCK were visibly up-regulated in the Ad-NONMMUGO148387 group. Our findings confirm that long non-coding RNA NONMMUG014387 can promote proliferation of Schwann cells surrounding the injury site through targeting Cthrc1 and activating the Wnt/PCP pathway.
基金financially supported by the National Natural Science Foundation of China,No.81371366(to HFW)Characteristic Innovation Project of Colleges and Universities in Guangdong Province of China,No.2018KTSCX075(to HFW)+3 种基金the Key Project of Social Development of Dongguan of China,No.20185071521640(to HFW)College Students’ Science and Technology Innovation Training Project,China,Nos.201810571058,GDMU2018024,GDMU2018056,GDMU2018061(to HFW)College Students’ Innovative Experimental Project in Guangdong Medical University,China,No.ZZDS001(to HFW)College Students’ Science and Technology Innovation Cultivation Project in Guangdong of China,No.pdjh2019b0217(to HFW)
文摘Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular mechanisms of lncRNAs in spinal cord injury(SCI),the expression signatures of lncRNAs were profiled using RNA sequencing(RNA-seq)technology in a Sprague-Dawley rat model of the 10th thoracic vertebra complete transection SCI.Results showed that 116 of 14,802 detected lncRNAs were differentially expressed,among which 16—including eight up-regulated(H19,Vof16,Hmox2-ps1,LOC100910973,Ybx1-ps3,Nnat,Gcgr,LOC680254)and eight down-regulated(Rmrp,Terc,Ngrn,Ppp2r2b,Cox6a2,Rpl37a-ps1,LOC360231,Rpph1)—demonstrated fold changes>2 in response to transection SCI.A subset of these RNA-seq results was validated by quantitative real-time PCR.The levels of 821 mRNAs were also significantly altered post-SCI;592 mRNAs were up-regulated and 229 mRNAs were down-regulated by more than 2-fold.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses showed that differentially expressed mRNAs were related to GO biological processes and molecular functions such as injury and inflammation response,wound repair,and apoptosis,and were significantly enriched in 15 KEGG pathways,including cell phagocytosis,tumor necrosis factor alpha pathway,and leukocyte migration.Our results reveal the expression profiles of lncRNAs and mRNAs in the rat spinal cord of a complete transection model,and these differentially expressed lncRNAs and mRNAs represent potential novel targets for SCI treatment.We suggest that lncRNAs may play an important role in the early immuno-inflammatory response after spinal cord injury.This study was approved by the Administration Committee of Experimental Animals,Guangdong Province,China.
基金supported by the National Natural Science Foundation of China,No.81600747(to YD)the Start-Up Foundation for Doctors of Liaoning Province,China,No.201501020(to YD)。
文摘Whether long non-coding RNA myocardial infarction-associated transcript is involved in oxygen-induced retinopathy remains poorly understood. To validate this hypothesis, we established a newborn mouse model of oxygen-induced retinopathy by feeding in an oxygen concentration of 75 ± 2% from postnatal day 8 to postnatal day 12, followed by in normal air. On postnatal day 11, the mice were injected with the myocardial infarction-associated transcript siRNA plasmid via the vitreous cavity to knockdown long non-coding RNA myocardial infarction-associated transcript. Myocardial infarction-associated transcript siRNA transcription significantly inhibited myocardial infarctionassociated transcript mRNA expression, reduced the phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor immunopositivities, protein and mRNA expression, and alleviated the pathological damage to the retina of oxygen-induced retinopathy mouse models. These findings suggest that myocardial infarction-associated transcript is likely involved in the retinal neovascularization in retinopathy of prematurity and that inhibition of myocardial infarction-associated transcript can downregulate phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor expression levels and inhibit neovascularization. This study was approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University, China(approval No. 2016 PS074 K) on February 25, 2016.
文摘In China, hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC), which is called HBV-related HCC (HBV-HCC), but the pathogenesis has not been clearly elu- cidated. Long non-coding RNAs (lncRNAs) have been paid increasing attention to, as an important regulatory molecule involved in many biological processes, as well as a variety of diseases. This study examined lncRNA that might play an important role in HBV-HCC pathogenesis by conducting lncRNA and mRNA profile comparison between HBV-HCC and normal liver tissues. The differentially ex- pressed lncRNA and mRNA profiles between HBV-HCC and normal liver tissues were analyzed by mi- croarrays. The potential protein-encoding gene regulated by lncRNA, and the biological function (gene ontology, pathway analysis) of the target gene were investigated. The results showed that the expression levels of lncRNA and mRNA in HBV-HCC tissues were different from those in normal liver tissues. As compared with normal liver tissue, 837 (4.30%) lncRNAs exhibited more than two-fold change (P〈0.05); 325 were up-regulated, and 512 were down-regulated; 991 (5.70%) mRNAs exhibited more than 2-fold change (P〈0.05); 733 were up-regulated and 258 were down-regulated in HBV-HCC tissue. Besides, there were 7 lncRNAs with above 10-fold elevation, 6 lncRNAs with above 10-fold decrease, 18 mRNAs with above 10-fold elevation and 11 mRNAs with above 10-fold decrease. 444 (53.05%) lncRNAs had their corresponding mRNAs, some of which were adjacent to lncRNAs. The biological analysis showed that the target gene of differentially expressed lncRNAs took part in the important bio- logical regulatory function. Target gene-related pathway analysis revealed the pathways in carcinoma and mitogen-activated protein kinase (MAPK) signaling pathways significantly changed in the HBV-HCC tissues as compared with normal liver tissues (P〈0.05). It was suggested that as compared with normal liver tissues, the expression of lncRNAs in HBV-HCC tissues changed significantly, and lncRNAs played a key role in the pathogenesis of HBV-HCC probably by mainly regulating the carci- noma-related signaling pathway and MAPK signaling pathways.
文摘Severe cerebral ischemia/reperfusion injury has been shown to induce high-level autophagy and neuronal death.Therefore,it is extremely important to search for a target that inhibits autophagy activation.Long non-coding RNA MEG3 participates in autophagy.However,it remains unclear whether it can be targeted to regulate cerebral ischemia/reperfusion injury.Our results revealed that in oxygen and glucose deprivation/reoxygenation-treated HT22 cells,MEG3 expression was obviously upregulated,and autophagy was increased,while knockdown of MEG3 expression greatly reduced autophagy.Furthermore,MEG3 bound mi R-181 c-5 p and inhibited its expression,while mi R-181 c-5 p bound to autophagy-related gene ATG7 and inhibited its expression.Further experiments revealed that mir-181 c-5 p overexpression reversed the effect of MEG3 on autophagy and ATG7 expression in HT22 cells subjected to oxygen and glucose deprivation/reoxygenation.In vivo experiments revealed that MEG3 knockdown suppressed autophagy,infarct volume and behavioral deficits in cerebral ischemia/reperfusion mice.These findings suggest that MEG3 knockdown inhibited autophagy and alleviated cerebral ischemia/reperfusion injury through the mi R-181 c-5 p/ATG7 signaling pathway.Therefore,MEG3 can be considered as an intervention target for the treatment of cerebral ischemia/reperfusion injury.This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Zhengzhou University,China(approval No.XF20190538)on January 4,2019.
基金supported by the National Natural Science Foundation of China (Grant No. 31660386)the Natural Science Foundation of Jiangxi Province for Distinguished Young Scholars (Grant No. 20171BCB23040)+1 种基金the Foundation of Jiangxi Educational Committee (Grant No. GJJ170193)the Sponsored Program for Distinguished Young Scholars in Jiangxi Normal University, China
文摘Long non-coding RNAs(lncRNAs) play important roles in response to various biotic and abiotic stresses. So far, systematic identification and characterization of lncRNAs have been reported in a few model plant species and major crops, but their roles in abiotic stress response have not yet been reported in common wild rice(Oryza rufipogon). Dongxiang wild rice(DXWR) possesses a high degree of drought resistance and has been well recognized as a precious genetic resource for drought resistant rice breeding. We presented the reference catalog of 1 655 novel lncRNA transcripts in DXWR using strand-specific RNA sequencing and bioinformatics approaches. Meanwhile, a total of 1092 lncRNAs were determined as differentially expressed lncRNAs under drought stress. Quantitative real-time PCR results exhibited a high concordance with RNA sequencing data, which confirmed that the expression patterns of lncRNAs based on RNA sequencing were highly reliable. Furthermore, 8 711 transcripts were predicted as target genes of the differentially expressed lncRNAs. Functional annotation analysis based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases showed that the target genes were significantly enriched in cellular and metabolic processes, cell part, binding and plant hormone signal transduction, as well as many other terms related to abiotic stress resistance. These results expanded our understanding of lncRNA biology and provided candidate regulators for genetic improvement of drought resistance in rice cultivars.
基金National Natural Science Foundation of China,No. 30700773,No. 81070378,and No. 81270561Sichuan Outstanding Youth Fund Project,No. 2015JQ0060。
文摘BACKGROUND Long non-coding RNAs(lncRNAs) have been shown to be associated with many tumors. However, the specific mechanism of lncRNAs in the occurrence and development of gastric cancer(GC) has not been fully elucidated.AIM To explore the expression level and molecular mechanism of HOXD-AS2 in GC tissues and cells, and analyze its significance in the prognosis of GC.METHODS Real-time quantitative PCR was used to detect the expression of HOXD-AS2 in 79 pairs of GC tissues and five cell lines. The pc HOXD-AS2 plasmid vector was constructed and transfected into SGC-7901 and SNU-1 GC cells. Matrigel Transwell and wound healing assays were used to confirm the effect of HOXDAS2 on invasion and migration of GC cells. Cell counting kit-8 assay and flow cytometry were used to verify the effect of HOXD-AS2 on the proliferation, cell cycle, and apoptosis of GC cells. The relevant regulatory mechanism between HOXD-AS2 and HOXD8 and PI3K/Akt signaling pathway was verified by Western blot analysis.RESULTS The low expression of lncRNA HOXD-AS2 was associated with lymph node metastasis and tumor-node-metastasis stage in GC. In vitro functional experiments demonstrated that overexpression of HOXD-AS2 inhibited GC cell progression. Mechanistic studies revealed that HOXD-AS2 regulated the expression of its nearby gene HOXD8 and inhibited the activity of the PI3K/Akt signaling pathway.CONCLUSION These results indicate that downregulation of HOXD-AS2 significantly promotes the progression of GC cells by regulating HOXD8 expression and activating the PI3K/Akt signaling pathway. HOXD-AS2 may be a novel diagnostic biomarker and effective therapeutic target for GC.
文摘Long non-coding RNAs(lnc RNAs) are a subgroup of non-coding RNA transcripts greater than 200 nucleotides in length with little or no protein-coding potential. Emerging evidence indicates that lnc RNAs may play important regulatory roles in the pathogenesis and progression of human cancers, including hepatocellular carcinoma(HCC). Certain lnc RNAs may be used as diagnostic or prognostic markers for HCC, a serious malignancy with increasing morbidity and high mortality rates worldwide. Therefore, elucidating the functional roles of lnc RNAs in tumors can contribute to a better understanding of the molecular mechanisms of HCC and may help in developing novel therapeutic targets. In this review, we summarize the recent progress regarding the functional roles of lnc RNAs in HCC and explore their clinical implications as diagnostic or prognostic biomarkers and molecular therapeutic targets for HCC.
基金supported by grants from National Health Commission Scientific Research Fund–Major Project of Zhejiang Medical and Health Science and Technology Plan(WKJ-ZJ-1901)National Natural Science Foundation of China(81001324 and 81373163)+3 种基金Natural Science Foundation of Zhejiang Province grant for“Outstanding Youth”(LR15H100001)interim starting Fund-ing from ZJPPHCommission of Science Technology of Minhang District(2019MHZ079)Minhang Scientific Research Found projects grant(2017MHJC02)。
文摘Background:Hepatectomy and liver transplantation(LT)are the two most commonly performed surgical procedures for various hepatic lesions.micro RNA(mi RNA)and long non-coding RNA(lnc RNA)have been gradually unveiled their roles as either biomarkers for early diagnosis or potentially therapeutic tools to manipulate gene expression in many disease entities.This review aimed to discuss the effects of mi RNA or lnc RNA in the hepatectomy and LT fields.Data sources:We did a literature search from 1990 through January 2018 to summarize the currently available evidence with respect to the effects of mi RNA and lnc RNA in liver regeneration after partial hepatectomy,as well as their involvement in several key issues related to LT,including ischemia-reperfusion injury,allograft rejection,tolerance,recurrence of original hepatic malignancies,etc.Results:Certain mi RNAs and lnc RNAs are actively involved in the regulation of various aspects of liver resection and transplantation.During the process of liver regeneration after hepatectomy,the expression of mi RNAs and lnc RNAs shows dynamic changes.Conclusions:It is now clear that mi RNAs and lnc RNAs orchestrate in various aspects of the pathophysiological process of LT and hepatectomy.Better understanding of the underlying mechanism and future clinical trials may strengthen their positions as either biomarkers or potential therapeutic targets in the management of complications after liver surgery.
文摘Objective To explore novel long non-coding RNA(lncRNA)molecular markers related to bladder cancer prognosis and to construct a prognostic prediction model for bladder cancer patients.Methods LncRNA expression data of patients with bladder cancer were downloaded from TCGA database.Univariate Cox regression and likelihood-based survival analysis were used to discover prognosis related lncRNAs.Functional studies of prognosis related lncRNAs were conducted by co-expression analysis and pathway enrichment analysis.Multivariate Cox regression analysis was used to establish risk score model,and Receiver Operating Characteristic analysis was used to determine the optimal cut-off point of the model.The risk score model was validated through Kaplan Meier estimation method and log-rank test.Results Seven prognosis related lncRNAs(OCIAD1-AS1,RP11-111 J6.2,AC079354.3,RP11-553 A21.3,RP11-598 F7.3,CYP4 F35 P and RP11-113 K21.4)which can predict survival of bladder cancer patient were discovered.Co-expression analysis and pathway analysis of these novel lncRNA signature and their target genes further revealed that these lncRNAs play important roles in the occurrence and development of bladder cancer.Additionally,a seven-lncRNA signature based risk score model for prognostic prediction of bladder cancer patients was established and validated.Notably,we identified the potential significance of two tumor-related antisense lncRNAs(OCIAD1-AS1 and RP11-553 A21.3)in the prognosis of bladder cancer.Conclusion Our results suggest that these lncRNA markers may serve as potential prognosis predictors for bladder cancer and deserve further functional verification studies.