Novel insights on oral squamous cell carcinoma management using long non-coding RNAs

Oral squamous cell carcinoma(OSCC)is one of the most prevalent forms of head and neck squamous cell carcinomas(HNSCC)with a poor overall survival rate(about 50%),particularly in cases of metastasis.RNA-based cancer biomarkers are a relatively advanced concept,and non-coding RNAs currently have shown promising roles in the detection and treatment of various malignancies.This review underlines the function of long non-coding RNAs(lncRNAs)in the OSCC and its subsequent clinical implications.LncRNAs,a class of non-coding RNAs,are larger than 200 nucleotides and resemble mRNA in numerous ways.However,unlike mRNA,lncRNA regulates multiple druggable and non-druggable signaling molecules through simultaneous interaction with DNA,RNA,proteins,or microRNAs depending on concentration and localization in cells.Upregulation of oncogenic lncRNAs and downregulation of tumor suppressor lncRNAs are evident in OSCC tissues and body fluids such as blood and saliva indicating their potential as valuable biomarkers.Targeted inhibition of candidate oncogenic lncRNAs or overexpression of tumor suppressor lncRNAs showed potential therapeutic roles in in-vivo animal models.The types of lncRNAs that are expressed differentially in OSCC tissue and bodily fluids have been systematically documented with specificity and sensitivity.This review thoroughly discusses the biological functions of such lncRNAs in OSCC cell survival,proliferation,invasion,migration,metastasis,angiogenesis,metabolism,epigenetic modification,tumor immune microenvironment,and drug resistance.Subsequently,we addressed the diagnostic and therapeutic importance of lncRNAs in OSCC pre-clinical and clinical systems,providing details on ongoing research and outlining potential future directions for advancements in this field.In essence,this review could be a valuable resource by offering comprehensive and current insights into lncRNAs in OSCC for researchers in fundamental and clinical domains.

Molecular mechanisms underlying roles of long non-coding RNA small nucleolar RNA host gene 16 in digestive system cancers

This editorial reviews the molecular mechanisms underlying the roles of the long non-coding RNA(lncRNA)small nucleolar RNA host gene 16(SNHG16)in digestive system cancers based on two recent studies on lncRNAs in digestive system tumors.The first study,by Zhao et al,explored how hBD-1 affects colon cancer,via the lncRNA TCONS_00014506,by inhibiting mTOR and promoting autophagy.The second one,by Li et al,identified the lncRNA prion protein testis specific(PRNT)as a factor in oxaliplatin resistance by sponging ZNF184 to regulate HIPK2 and influence colorectal cancer progression and chemoresistance,suggesting PRNT as a potential therapeutic target for colorectal cancer.Both of these two articles discuss the mechanisms by which lncRNAs contribute to the development and progression of digestive system cancers.As a recent research hotspot,SNHG16 is a typical lncRNA that has been extensively studied for its association with digestive system cancers.The prevailing hypothesis is that SNHG16 participates in the development and progression of digestive system tumors by acting as a competing endogenous RNA,interacting with other proteins,regulating various genes,and affecting downstream target molecules.This review systematically examines the recently reported biological functions,related molecular mechanisms,and potential clinical significance of SNHG16 in various digestive system cancers,and explores the relationship between SNHG16 and digestive system cancers.The findings suggest that SNHG16 may serve as a potential biomarker and therapeutic target for human digestive system cancers.

Clinical application value of long non-coding RNAs signatures of genomic instability in predicting prognosis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)presents challenges due to its high recurrence and metastasis rates and poor prognosis.While current clinical diagnostic and prognostic indicators exist,their accuracy remains imperfect due to their biol-ogical complexity.Therefore,there is a quest to identify improved biomarkers for HCC diagnosis and prognosis.By combining long non-coding RNA(lncRNA)expression and somatic mutations,Duan et al identified five representative lncRNAs from 88 lncRNAs related to genomic instability(GI),forming a GI-derived lncRNA signature(LncSig).This signature outperforms previously re-ported LncSig and TP53 mutations in predicting HCC prognosis.In this editorial,we comprehensively evaluate the clinical application value of such prognostic evaluation model based on sequencing technology in terms of cost,time,and practicability.Additionally,we provide an overview of various prognostic models for HCC,aiding in a comprehensive understanding of research progress in pro-gnostic evaluation methods.

Role of long non-coding RNAs in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is emerging as a common cause of chronic liver disease in children and adults.NAFLD can progress to steatohepa-titis and potentially even hepatocellular carcinoma.Early identification of pati-ents at risk for progressive disease is crucial for managing NAFLD.Recent studies have identified long noncoding RNAs(lncRNAs),circular RNAs,and microRNAs as playing important roles in the pathogenesis of NAFLD.These noncoding RNAs are involved in modulating several metabolic pathways such as hepatic glucose and lipid metabolism,oxidative stress,and even carcinogenesis.Elevated levels of lncARSR and lncRNA nuclear-enriched abundant transcript 1 have been found in patients with NAFLD.In addition,lncRNAs such as PRYP4-3 and RP11-128N14.5 can distinguish patients with NAFLD from healthy indi-viduals.Increased MEG3 expression has been observed in both NAFLD and non-alcoholic steatohepatitis,suggesting that it may help predict patients at risk for disease progression.With advances in transcriptomics,we may discover additional targets to help in the identification and prognostication of NAFLD.

Navigating the labyrinth of long non-coding RNAs in colorectal cancer:From chemoresistance to autophagy

Long non-coding RNAs(lncRNAs),with transcript lengths exceeding 200 nucleotides and little or no protein-coding capacity,have been found to impact colorectal cancer(CRC)through various biological processes.LncRNA expression can regulate autophagy,which plays dual roles in the initiation and progression of cancers,including CRC.Abnormal expression of lncRNAs is associated with the emergence of chemoresistance.Moreover,it has been confirmed that targeting autophagy through lncRNA regulation could be a viable approach for combating chemoresistance.Two recent studies titled“Human β-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long non-coding RNA TCONS_00014506”and“Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription”revealed novel insights into lncRNAs associated with autophagy and oxaliplatin resistance in CRC,respectively.In this editorial,we particularly focus on the regulatory role of lncRNAs in CRC-related autophagy and chemoresistance since the regulation of chemotherapeutic sensitivity by intervening with the lncRNAs involved in the autophagy process has become a promising new approach for cancer treatment.

Expression and significant roles of the long non-coding RNA CASC19/miR-491-5p/HMGA2 axis in the development of gastric cancer

BACKGROUND Gastric cancer(GC)is a common malignant tumor,long non-coding RNA and microRNA(miRNA)are important regulators that affect tumor proliferation,metastasis and chemotherapy resistance,and thus participate in tumor progression.CASC19 is a new bio-marker which can promote tumor invasion and metastasis.However,the mechanism by which CASC19 affects the progression of GC through miRNA is not clear.AIM To explore the role of the CASC19/miR-491-5p/HMGA2 regulatory axis in GC.METHODS To explore the expression and prognosis of CASC19 in GC through clinical samples,and investigate the effects of inhibiting CASC19 on the proliferation,migration,invasion and other functions of GC cells through cell counting Kit-8(CCK-8),ethynyldeoxyuridine,Wound healing assay,Transwell,Western blot and flow cytometry experiments.The effect of miR-491-5p and HMGA2 in GC were also proved.The regulatory relationship between CASC19 and miR-491-5p,miR-491-5p and HMGA2 were validated through Dual-luciferase reporter gene assay and reverse transcription PCR.Then CCK-8,Transwell,Wound healing assay,flow cytometry and animal experiments verify the role of CASC19/miR-491-5p/HMGA2 regulatory axis.RESULTS The expression level of CASC19 is related to the T stage,N stage,and tumor size of patients.Knockdown of the expression of CASC19 can inhibit the ability of proliferation,migration,invasion and EMT conversion of GC cells,and knocking down the expression of CASC19 can promote the apoptosis of GC cells.Increasing the expression of miR-491-5p can inhibit the proliferation of GC cells,miR-491-5p mimics can inhibit EMT conversion,and promote the apoptosis of GC cells,while decreasing the expression of miR-491-5p can promote the proliferation and EMT conversion and inhibit the apoptosis of GC cells.The expression of HMGA2 in GC tissues is higher than that in adjacent tissues.At the same time,the expression level of HMGA2 is related to the N and T stages of the patients.Reducing the level of HMGA2 can promote cell apoptosis and inhibit the proliferation of GC cells.Cell experiments and animal experiments have proved that CASC19 can regulates the expression of HMGA2 through miR-491-5p,thereby affecting the biological functions of GC.CONCLUSION CASC19 regulates the expression of HMGA2 through miR-491-5p to affect the development of GC.This axis may serve as a potential biomarker and therapeutic target of GC.

Construction of prognostic markers for gastric cancer and comprehensive analysis of pyroptosis-related long non-coding RNAs

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.

Involvement of long non-coding RNAs in pear fruit senescence under high-and low-temperature conditions

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.

Expression profile of long non-coding RNAs in the intestine of black rockfish Sebastes schlegelii in response to Edwardsiella tarda infection

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.

Molecular hallmarks of long non-coding RNAs in aging and its significant effect on aging-associated diseases

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.

Identification and Characterization of Long Non-Coding RNAs Involved in Sex-Related Gene Regulation in Kelp Saccharina japonica

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.

Regulatory mechanisms of long non-coding RNAs

Long non-coding RNAs(lncRNAs) belong to a large and complex family of RNAs, which play many important roles in regulating gene expression. However, the mechanism underlying the dynamic expression of lncRNAs is still not very clear. In order to identify lncRNAs and clarify the mechanisms involved, we collected basic information and highlighted the mechanisms underlying lncRNA expression and regulation. Overall, lncRNAs are regulated by several similar transcription factors and protein-coding genes. Epigenetic modification(DNA methylation and histone modification) can also downregulate lncRNA levels in tissues and cells. Moreover, lncRNAs may be degraded or cleaved via interaction with miRNAs and miRNAassociated protein complexes. Furthermore, alternative RNA splicing(AS) may play a significant role in the post-transcriptional regulation of lncRNAs.

Bioinformatics Analysis and Experimental Verification of Prognostic and Biological Significance of Autophagy-Related Long Non-Coding RNAs in Gastric Carcinoma

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.

Long Non-coding RNA PCED1B Antisense RNA 1 Promotes Cell Proliferation and Invasion in Hepatocellular Carcinoma by Regulating the MicroRNA-34a/CD44 Axis

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.

Non-coding RNAs in acute ischemic stroke:from brain to periphery

Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

Long non-coding RNA VPS9D1-AS1对乳腺癌细胞恶性行为的影响和机制

目的探讨长链非编码RNA(LncRNA)VPS9D1-AS1对乳腺癌细胞恶性行为的影响和机制。方法收集49例接受手术的乳腺癌患者的乳腺癌组织和癌旁组织,体外培养人正常乳腺上皮细胞MCF-10A和乳腺癌细胞系MCF-7、T47D、BT549,采用实时荧光定量PCR(RT-qPCR)检测miR-4695-5p及LncRNA VPS9D1-AS1表达水平;选择MCF-7细胞分别转染si-NC、si-LncRNA VPS9D1-AS1、pcDNA、pcDNA-LncRNA VPS9D1-AS1、miR-NC、miR-4695-5p模拟物、anti-miR-NC+si-LncRNA VPS9D1-AS1、anti-miR-4695-5p+si-LncRNA VPS9D1-AS1,采用RT-qPCR检测MCF-7细胞中LncRNA VPS9D1-AS1、miR-4695-5p表达水平,CCK-8和Transwell实验评估细胞存活率和迁移侵袭数,蛋白质印记法检测IL-6、MMP2、MMP9蛋白水平;双荧光素酶实验证实LncRNA VPS9D1-AS1与miR-4695-5p的靶向关系。结果LncRNA VPS9D1-AS1在乳腺癌组织和MCF-7、T47D、BT549细胞系中表达上调(P<0.05),miR-4695-5p表达下调(P<0.05),MCF-7细胞中LncRNA VPS9D1-AS1、miR-4695-5p变化最明显,选择MCF-7细胞进行后续实验;转染LncRNA VPS9D1-AS1后,MCF-7细胞存活率、细胞迁移和侵袭数以及IL-6、MMP2、MMP9蛋白水平降低(P<0.05);转染miR-4695-5p模拟物后,miR-4695-5p表达升高(P<0.05),MCF-7细胞存活率、细胞迁移和侵袭数及IL-6、MMP2、MMP9蛋白水平降低(P<0.05);转染pcDNA-LncRNA VPS9D1-AS1后,MCF-7细胞中miR-4695-5p表达下降(P<0.05);共转染anti-miR-4695-5p+si-LncRNA VPS9D1-AS1后,MCF-7细胞存活率、迁移数和侵袭数及IL-6、MMP2、MMP9蛋白水平升高(P<0.05)。结论干扰LncRNA VPS9D1-AS1通过靶向上调miR-4695-5p抑制促炎因子IL-6表达,进而抑制乳腺癌MCF-7细胞增殖、迁移及侵袭。

Diagnostic and prognostic potential of tissue and circulating long non-coding RNAs in colorectal tumors

Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC.

Functional role of long non-coding RNA CASC19/miR-140-5p/CEMIP axis in colorectal cancer progression in vitro

BACKGROUND Long non-coding RNAs(lncRNAs) are widely involved in tumor regulation.Nevertheless, the role of the lncRNA cancer susceptibility 19(CASC19) in colorectal cancer(CRC) has yet to be fully clarified.AIM To explore the effect of CASC19 on proliferation and metastasizing ability of CRC cells.METHODS CASC19 expression in human CRC tissues, pair-matched adjacent normal colon tissues, and CRC cells was detected using quantitative real-time PCR(qRT-PCR).CASC19 expression, as well as its relation to overall survival, was extrapolated by Kaplan-Meier survival analysis together with multivariable Cox regression assay.In vitro experiments were performed to confirm whether CASC19 regulates CRC cell invasion, migration, proliferation, and apoptosis.RESULTS CASC19 expression was markedly upregulated in CRC tissues and CRC cell lines(P < 0.05). qRT-PCR revealed that CASC19 expression was higher in 25 tissue samples from patients with aggressive CRC compared with the 27 tissue samples from patients with nonaggressive CRC(P < 0.05). Higher CASC19 expression was associated with poorer patient prognoses. Furthermore, in vitro experiments demonstrated that CASC19 overexpression enhanced CRC cell invasion,migration, and proliferation. CASC19 overexpression enhanced the expression of cell migration inducing hyaluronidase 1(CEMIP) and epithelial-mesenchymal transition markers. MiR-140-5 p was found to be able to bind directly to CASC19 and CEMIP. Overexpression of miR-140-5 p reversed the effect of CASC19 on cellproliferation and tumor migration, as well as suppressed CASC19-induced CEMIP expression.CONCLUSION CASC19 positively regulates CEMIP expression through targeting miR-140-5 p.CASC19 may possess an oncogenic function in CRC progression, highlighting its potential as an essential biomarker in CRC diagnosis and therapy.

MicroRNAs and long non-coding RNAs in liver surgery:Diagnostic and therapeutic merits

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.

Effects of long non-coding RNA Opa-interacting protein 5 antisense RNA 1 on colon cancer cell resistance to oxaliplatin and its regulation of micro RNA-137

BACKGROUND The incidence of colon cancer(CC)is currently high,and is mainly treated with chemotherapy.Oxaliplatin(L-OHP)is a commonly used drug in chemotherapy;however,long-term use can induce drug resistance and seriously affect the prognosis of patients.Therefore,this study investigated the mechanism of Opainteracting protein 5 antisense RNA 1(OIP5-AS1)on L-OHP resistance by determining the expression of OIP5-AS1 and micro RNA-137(miR-137)in CC cells and the effects on L-OHP resistance,with the goal of identifying new targets for the treatment of CC.AIM To study the effects of long non-coding RNA OIP5-AS1 on L-OHP resistance in CC cell lines and its regulation of miR-137.METHODS A total of 114 CC patients admitted to China-Japan Union Hospital of Jilin University were enrolled,and the expression of miR-137 and OIP5-AS1 in tumor tissues and corresponding normal tumor-adjacent tissues was determined.The influence of OIP5-AS1 and miR-137 on the biological behavior of CC cells was evaluated.Resistance to L-OHP was induced in CC cells,and their activity was determined and evaluated using cell counting kit-8.Flow cytometry was used to analyze the apoptosis rate,Western blot to determine the levels of apoptosisrelated proteins,and dual luciferase reporter assay combined with RNA-binding protein immunoprecipitation to analyze the relationship between OIP5-AS1 and miR-137.RESULTS OIP5-AS1 was up-regulated in CC tissues and cells,while miR-137 was downregulated in CC tissues and cells.OIP5-AS1 was inversely correlated with miR-137(P<0.001).Silencing OIP5-AS1 expression significantly hindered the proliferation,invasion and migration abilities of CC cells and markedly increased the apoptosis rate.Up-regulation of miR-137 expression also suppressed these abilities in CC cells and increased the apoptosis rate.Moreover,silencing OIP5-AS1 and up-regulating miR-137 expression significantly intensified growth inhibition of drug-resistant CC cells and improved the sensitivity of CC cells to LOHP.OIP5-AS1 targetedly inhibited miR-137 expression,and silencing OIP5-AS1 reversed the resistance of CC cells to L-OHP by promoting the expression of miR-137.CONCLUSION Highly expressed in CC,OIP5-AS1 can affect the biological behavior of CC cells,and can also regulate the resistance of CC cells to L-OHP by mediating miR-137 expression.