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.

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.

Characterization of N6-methyladenosine long non-coding RNAs in sporadic congenital cataract and age-related cataract

AIM:To characterize the N6-methyladenosine(m6A)modification patterns in long non-coding RNAs(lncRNAs)in sporadic congenital cataract(CC)and age-related cataract(ARC).METHODS:Anterior capsule of the lens were collected from patients with CC and ARC.Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing were performed to identify m6A-tagged lncRNAs and lncRNAs expression.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and Gene Ontology annotation were used to predict potential functions of the m6A-lncRNAs.RESULTS:Large amount of m6A peaks within lncRNA were identified for both CC and ARC,while the level was much higher in ARC(49870 peaks)than that in CC(18688 peaks),yet those difference between ARC in younger age group(ARC-1)and ARC in elder age group(ARC-2)was quite slight.A total of 1305 hypermethylated and 1178 hypomethylated lncRNAs,as well as 182 differential expressed lncRNAs were exhibited in ARC compared with CC.On the other hand,5893 hypermethylated and 5213 hypomethylated lncRNAs,as well as 155 significantly altered lncRNA were identified in ARC-2 compared with ARC-1.Altered lncRNAs in ARC were mainly associated with the organization and biogenesis of intracellular organelles,as well as nucleotide excision repair.CONCLUSION:Our results for the first time present an overview of the m6A methylomes of lncRNA in CC and ARC,providing a solid basis and uncovering a new insight to reveal the potential pathogenic mechanism of CC and ARC.

Non-coding RNA as future target for diagnose and treatment of perineural invasion in cancers

Perineural invasion(PNI),a particularly insidious form of tumor metastasis distinct from hematogenous or lymphatic spread,has the capacity to extend well beyond the primary tumor site,infiltrating distant regions devoid of lymphatic or vascular structures.PNI often heralds a decrease in patient survival rates and is recognized as an indicator of an unfavorable prognosis across a variety of cancers.Despite its clinical significance,the underlying molecular mechanisms of PNI remain elusive,complicating the development of specific and efficacious diagnostic and therapeutic strategies.In the realm of cancer research,non-coding RNAs(ncRNAs)have attracted considerable attention due to their multifaceted roles and cancer-specific expression profiles,positioning them as promising candidates for applications in cancer diagnostics,prognostics,and treatment.Among the various types of ncRNAs,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)have emerged as influential players in PNI.Their involvement is increasingly recognized as a contributing factor to tumor progression and therapeutic resistance.Our study synthesizes and explores the diverse functions and mechanisms of ncRNAs in relation to PNI in cancer.This comprehensive review aims to shed light on cutting-edge perspectives that could pave the way for innovative diagnostic and therapeutic approaches to address the challenges posed by PNI in oncology.

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.

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.

Long non-coding RNAs with essential roles in neurodegenerative disorders

Recently,with the advent of high-resolution and high-throughput sequencing technologies,an increasing number of long non-coding RNAs(lncRNAs)have been found to be involved in the regulation of neuronal function in the central nervous system with specific spatiotemporal patterns,across different neurodegenerative diseases.However,the underlying mechanisms of lncRNAs during neurodegeneration remain poorly understood.This review provides an overview of the current knowledge of the biology of lncRNAs and focuses on introducing the latest identified roles,regulatory mechanisms,and research status of lncRNAs in Alzheimer's disease,Parkinson's disease,Huntington's disease,and amyotrophic lateral sclerosis.Finally,this review discusses the potential values of lncRNAs as diagnostic biomarkers and therapeutic targets for neurodegenerative diseases,hoping to provide broader implications for developing effective treatments.

Urgent need for prognostic markers for hepatocellular carcinoma in the light of genomic instability and non-coding RNA signatures

In this editorial,we comment on an original article by Duan et al.Despite ad-vancements in the diagnosis and treatment of hepatocellular carcinoma(HCC),the identification of suitable prognostic factors remains challenging.In their paper,Duan et al identified long non-coding RNAs(LncRNAs)to quantify ge-nomic instability(GI)by combining LncRNA expression and somatic mutation profiles.They confirmed that the GI-derived LncRNA signature(GI-LncSig)could be an independent prognostic factor with the area under the curve of 0.773.Fur-thermore,the authors stated that GI-LncSig may have a better predictive perfor-mance than TP53 mutation status alone.However,studies exploring genetic markers for predicting the prognosis of HCC are crucial for identifying thera-peutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of liver 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.

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.

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.

Long non-coding RNA GATA6-AS1 is mediated by N6-methyladenosine methylation and inhibits the proliferation and metastasis of gastric cancer

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.

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.

Tissue-specific differential expression of novel genes and long intergenic non-coding RNAs in humans with extreme response to evoked endotoxemia

Objective Cytokine responses to activation of innate immunity differ between individuals,yet the genomic and tissue-specific transcriptomic determinants of inflammatory responsiveness are not well understood. We hypothesized that tissue-specific mRNA and long intergenic non-coding RNA (lincRNA) induction differs between individuals with divergent evoked inflammatory responses.

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.

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.

Emerging roles of non-coding RNAs in colorectal cancer oxaliplatin resistance and liquid biopsy potential

Colorectal cancer(CRC)is one of the most common malignancies of the digestive tract,with the annual incidence and mortality increasing consistently.Oxaliplatinbased chemotherapy is a preferred therapeutic regimen for patients with advanced CRC.However,most patients will inevitably develop resistance to oxaliplatin.Many studies have reported that non-coding RNAs(ncRNAs),such as microRNAs,long non-coding RNAs,and circular RNAs,are extensively involved in cancer progression.Moreover,emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation,and by epigenetic modification.In this review,we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin.Furthermore,we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy.This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.

Haplotype analysis of long-chain non-coding RNA NONHSAT102891 promoter polymorphisms and depression in Chinese individuals: A case-control association study

BACKGROUND Our previous study reported that the single-nucleotide polymorphism(SNP)rs155979 GC in the promoter region of long-chain non-coding RNA(lncRNA)NONHSAT102891 affects depression susceptibility in a Chinese population.AIM To explored associations of two SNPs and haplotypes in the lncRNA NONHSAT102891 promoter region with depression susceptibility in Chinese population.METHODS This this case-control association study was approved by the Ethics Committee of Chengdu Medical College(approval number:201815).Patient diagnosis was based on DSM-IV criteria.We selected a total of 480 patients with depression and 329 healthy controls with no history of psychopathology,and performed genotyping of two SNPs by extracting peripheral venous blood samples from the subjects.The function of the two lncRNA NONHSAT102891 promoter G/C and A/T haplotypes was detected by dual-luciferase reporter assays of human embryonic kidney 293T transfected cells.RESULTS Stratified analysis of clinical and genotypic characteristics of our cohort showed that the degree of mild depressive episodes associated with the rs6230 TC/CC genotype increased by 1.59 times[TC/CC vs TT:odds ratio(OR)=1.59,95%confidence interval(CI):1.08-2.35,P=0.019].The haploid analysis revealed linkage disequilibrium between rs3792747 and rs6230,and the double SNP CG haplotype was more common in the control group compared to case group,indicating that this haplotype significantly reduced the risk of depression(C/G vs T/A:OR=0.42,95%CI:0.21-0.83,P=0.01).There was no significant difference in the dual-luciferase reporter activity of the G/C and A/T haplotypes compared with the control group(P>0.05),indicating that the double SNP haplotype has no transcrip-tional activity.CONCLUSION The rs3792747 and rs6230 CG haplotypes of the lncRNA NONHSA T102891 promoter may be related to a reduced risk of depression in the Han Chinese population.

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.