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.

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.

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.

Behind the curtain of non-coding RNAs; long non-coding RNAs regulating hepatocarcinogenesis

Hepatocellular carcinoma(HCC) is one of the most common and aggressive cancers worldwide. HCC is the fifth common malignancy in the world and the second leading cause of cancer death in Asia. Long non-coding RNAs(lncRNAs) are RNAs with a length greater than 200 nucleotides that do not encode proteins. lncRNAs can regulate gene expression and protein synthesis in several ways by interacting with DNA, RNA and proteins in a sequence specific manner. They could regulate cellular and developmental processes through either gene inhibition or gene activation. Many studies have shown that dysregulation of lncRNAs is related to many human diseases such as cardiovascular diseases, genetic disorders, neurological diseases, immune mediated disorders and cancers. However, the study of lncRNAs is challenging as they are poorly conserved between species, their expression levels aren't as high as that of m RNAs and have great interpatient variations. The study of lncRNAs expression in cancers have been a breakthrough as it unveils potential biomarkers and drug targets for cancer therapy and helps understand the mechanism of pathogenesis. This review discusses many long non-coding RNAs and their contribution in HCC, their role in development, metastasis, and prognosis of HCC and how to regulate and target these lncRNAs as a therapeutic tool in HCC treatment in the future.

Role of long non-coding RNA in cells: Example of the <i>H</i>19/<i>IGF</i>2 locus

In the past decade, studies of non-coding RNAs increase. Non-coding RNAs are divided in two classes: small and long non-coding RNA. It was shown that long non-coding RNAs regulate expression of 70% of genes. Long non-coding RNAs are involved in several cellular processes like epigenetic regulation, dosage compensation, alternative splicing and stem cells maintenance for example. Misregulations of their expression induce diseases such as developmental syndrome or cancer. In this review, we describe some functions of long non-coding RNA in cells. Furthermore, we study the H19/IGF2 cluster: an imprinted genomic locus located on chromosome 11p15.5. Genomic imprinting allows gene expression from a single allele in a parent-origin-dependent manner. This cluster encode for the first long non-coding RNA identified: H19. In 1990, it was established that H19 functions as a riboregulator. Recently, it was shown that H19 is a precursor of microRNA (hsa-miR-675), and several news transcripts were identified at the H19/IGF2 locus. So, the complexity of this locus increasing, in this review, we summarize our current understanding about the H19/IGF2 cluster both in terms of transcription as well as in terms of functions in cells. We highlight the involvement of H19, its new antisense transcript 91H and its microRNA, in the regulation of IGF receptor function and in cell cycle progression.

Expression Profile of Altered Long Non-coding RNAs in Patients with HBV-associated Hepatocellular Carcinoma

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.

Danhongqing formula alleviates cholestatic liver fibrosis by downregulating long non-coding RNA H19 derived from cholangiocytes and inhibiting hepatic stellate cell activation

Objective:This study explores the mechanism of action of Danhongqing formula(DHQ),a compoundbased Chinese medicine formula,in the treatment of cholestatic liver fibrosis.Methods:In vivo experiments were conducted using 8-week-old multidrug resistance protein 2 knockout(Mdr2-/-)mice as an animal model of cholestatic liver fibrosis.DHQ was administered orally for 8 weeks,and its impact on cholestatic liver fibrosis was evaluated by assessing liver function,liver histopathology,and the expression of liver fibrosis-related proteins.Real-time polymerase chain reaction,Western blot,immunohistochemistry and other methods were used to observe the effects of DHQ on long non-coding RNA H19(H19)and signal transducer and activator of transcription 3(STAT3)phosphorylation in the liver tissue of Mdr2-/-mice.In addition,cholangiocytes and hepatic stellate cells(HSCs)were cultured in vitro to measure the effects of bile acids on cholangiocyte injury and H19 expression.Cholangiocytes overexpressing H19 were constructed,and a conditioned medium containing H19 was collected to measure its effects on STAT3 protein expression and cell activation.The intervention effect of DHQ on these processes was also investigated.HSCs overexpressing H19 were constructed to measure the impact of H19 on cell activation and assess the intervention effect of DHQ.Results:DHQ alleviated liver injury,ductular reaction,and fibrosis in Mdr2-/-mice,and inhibited H19expression,STAT3 expression and STAT3 phosphorylation.This formula also reduced hydrophobic bile acid-induced cholangiocyte injury and the upregulation of H19,inhibited the activation of HSCs induced by cholangiocyte-derived conditioned medium,and decreased the expression of activation markers in HSCs.The overexpression of H19 in a human HSC line confirmed that H19 promoted STAT3 phosphorylation and HSC activation,and DHQ was able to successfully inhibit these effects.Conclusion:DHQ effectively alleviated spontaneous cholestatic liver fibrosis in Mdr2-/-mice by inhibiting H19 upregulation in cholangiocytes and preventing the inhibition of STAT3 phosphorylation in HSC,thereby suppressing cell activation.

Exosome-transported IncRNA H19 regulates insulin-like growth factor-1 via the H19/let-7a/insulin-like growth factor-1 receptor axis in ischemic stroke

LncRNA(long non-coding RNA) H19 is a transcript of the H19 gene that is expressed during embryogenesis.We previously discove red a role for circular lncRNA H19 in the onset and prognosis of cerebral ischemic stroke.In this study,we used serum from patients with ischemic stroke,and mouse and cell culture models to elucidate the roles of plasma and neuronal exosomes in the regulatory effect of lncRNA H19 on insulin-like growth factor-1 and its mechanism in ischemic stroke,using western blotting,quantitative real-time polymerase chain reaction,and enzyme-linked immunosorbent assays.Plasma exosomal IncRNA H19 was negatively associated with blood levels of insulin-like growth factor-1 in samples from patients with cerebral ischemic stroke.In a mouse model,levels of exosomal IncRNA H19 were positively correlated with plasma and cerebral lncRNA H19.In a cell co-culture model,we confirmed that IncRNA H19 was transported from neuro ns to astrocytes by exosomes to induce downregulation of insulin-like growth factor-1 through the H19/let-7 a/insulin-like growth factor-1 receptor axis.This study provides the first evidence for the transpo rtation of IncRNA H19 by exosomes and the relationship between IncRNA H19 and insulinlike growth factor-1.

类风湿关节炎患者血清长链非编码RNA HOTAIR、XIST和H19表达研究

目的探讨3种长链非编码RNA(lncRNA) HOTAIR、XIST和H19在类风湿关节炎(RA)、系统性红斑狼疮(SLE)和健康人对照组血清中的差异表达。方法收取50例RA疾病组、50例SLE疾病对照组和60例健康人对照组血清,共160例血清标本,提取血清总RNA,利用RT-qPCR方法分析HOTAIR、XIST和H19 3种lncRNA表达情况。用Spearman相关性分析探讨RA患者疾病活动指数(DAS28)与HOTAIR表达量的相关性。结果 RA组与健康人对照组和SLE疾病对照组相比,血清HOTAIR表达量显著增加(P<0.01),XIST在RA和对照组之间表达量差异无统计学意义; RA患者血清中HOTAIR表达值与DAS28评分呈正相关(R^2=0.27,P=0.002),且DAS28评分≥5.1的疾病高度活动组的HOTAIR表达值显著高于3.2<DAS28评分<5.1的疾病活动组(P<0.01);血清HOTAIR表达量与血清C反应蛋白(CRP)存在正相关关系(R^2=0.192,P=0.002)。结论LncRNA HOTAIR在RA患者血清中的表达量显著性升高且与DAS28评分呈显著正相关关系,血清中HOTAIR有可能成为诊断RA的潜在生物标志物。

Plant Long ncRNAs: A New Frontier for Gene Regulatory Control

Long non-coding RNA (lncRNA) refers to an over 200 nt functional RNA molecule that will not be translated into protein. Previously thought to be dark matters of the genome, lncRNAs have been gradually recognized as crucial gene regulators. Although tremendous progress has been made in animals and human, the study of lncRNAs in plant is still in its infancy. Here, we reviewed the biogenesis and regulation mechanisms of lncRNAs and summarized the achievements that have been made in plant lncRNA identification and functional characterization. Genome-wide identification has uncovered large amount of lncRNAs in Arabidopsis, Rice, Maize and Wheat, and more information from other plant species will be expected with the aid of deep sequencing technologies. Similar to other species, LncRNA-mediated gene regulation also widely exists in plants, even though only a few functionally characterized examples are available. Up to now, at least four divergent lncRNA-mediated regulation mechanisms have been unraveled, including target mimicry, transcription interference, PRC2 associated histone methylation and DNA methylation. lncRNAs may be involved in the regulation of flowering, male sterility, nutrition metabolism, biotic and abiotic stress response in plants.

Mechanism of lncRNA SNHG19 miR-299-5p MAPK6 signaling axis promoting metastasis of non-small cell lung cancer cells

Objective The aim of this study was to explore the mechanism behind lncRNA small nucleolar RNA host gene 19(lncRNA SNHG19)/microrNA-299-5P(miR-299-5p)/mitogen-activated protein kinase 6(MAPK6)signaling axis promoting metastasis of non-small cell lung cancer(NSCLC).Methods To analyze the abnormal expression of lncRNAs in NSCLC,50 surgically resected NSCLC and adjacent tissue samples were collected from August 2021 to August 2022.The mRNA expression levels of lncRNA SNHG19,Mir-299-5p,and MAPK6 were detected by qRT-PCR.The functions of lncRNA SNHG19,Mir-299-5p and MAPK6 were investigated by CCK-8,clone formation,EdU,scratch,Transwell western blotting(WB)and in vivo xenograft assay.RNA fluorescence in-situ hybridization(FISH),RNA pull-down,dual luciferase reporter,and RNA co-immunoprecipitation assays were used to explore the mechanism of action between lncRNA SNHG19,miR-299-5p,and MAPK6.Results High expression of lncRNA SNHG19 was correlated with poor prognosis,tumor size,lymph node metastasis,and TNM stage in NSCLC patients(P<0.05).Cell function experiments showed that lncRNA SNHG19 could improve the proliferation,clone formation,migration,and invasion ability of A549 cells both in vitro and in vivo(all P<0.05)and increased the relative expression levels of vimentin and MAPK6(P<0.05).The relative expression level of E-cadherin was decreased(P<0.05).lncRNA SNHG19 can interact with Mir-299-5p and regulate the expression level of MAPK6.Conclusion lncRNA SNHG19 is upregulated in NSCLC tissues and cells,and its high expression is associated with tumor progression and poor survival.Moreover,it can act as a molecular sponge for Mir-299-5p to regulate MAPK6 expression and promote the proliferation and metastasis of A549 cells.

Evaluation of autophagy-related genes and lncRNAs signature for prognositic prediction in thyroid carcinoma via bioinformatics analysis

Autophagy plays a significant role in the pathogenesis and prognosis of thyroid carcinoma.The role of autophagy-related genes and long non-coding RNAs,as well as the risk model of thyroid carcinoma patients were investigated to predict clinical outcome of thyroid carcinoma.Different expression of autophagy-related genes and long non-coding RNAs in thyroid carcinoma patients was identified in The Cancer Genome Atlas database.Functional enrichment analysis and gene set enrichment analysis was used to hint the mechanism that autophagy might act in thyroid carcinoma.Univariate and multivariate Cox regression analyses were performed for screening the prognostic autophagy-related genes and long non-coding RNAs to construct prognostic related risk model.thyroid carcinoma patients were divided into the low-risk and high-risk groups.The overall survival time was both shorter in the high-risk groups than that in the low-risk groups.As for autophagy-related genes prognostic risk model,age and autophagy-related genes risk score are independent prognostic factors that affect the survival of thyroid carcinoma.ATIC and CDKN2A expression was closely related to pathological stage and T status,DNAJB1 expression was closely related to M status,age and gender.While autophagy-associated long non-coding RNA related prognostic risk model consequently demonstrated that the long non-coding RNA risk score could significantly predict the survival rate of thyroid carcinoma patients with areas under the curve of 0.972.gene set enrichment analysis presented that a total of 16 gene sets including 10 up-regulated and 6 down-regulated gene sets were significantly enriched.The autophagy-related genes and long non-coding RNAs based prognostic risk models are a reliable forecasting tool for thyroid carcinoma patients.

The long non-coding RNA DANA2 positively regulates drought tolerance by recruitingERF84 to promote JMJ29-mediated histone demethylation

Tens of thousands of long non-coding RNAs have been uncovered in plants,but few of them have been comprehensively studied for their biological function and molecular mechanism of their mode of action.Here,we show that the Arabidopsis long non-coding RNA DANA2 interacts with an AP2/ERF transcription factor ERF84 in the cell nucleus and then affects the transcription of JMJ29 that encodes a Jumonji C domain-containing histone H3K9 demethylase.Both RNA sequencing(RNA-seq)and genetic analyses demonstrate that DANA2 positively regulates drought stress responses through JMJ29.JMJ29 positively regulates the expression of ERF15 and GOLS2 by modulation of H3K9me2 demethylation.Accordingly,mutation of JMJ29 causes decreased ERF15 and GOLS2 expression,resulting in impaired drought tolerance,in agreement with drought-sensitive phenotypes of dana2 and erf84 mutants.Taken together,these results demonstrate that DANA2 is a positive regulator of drought response and works jointly with the transcriptional activator ERF84 to modulate JMJ29 expression in plant response to drought.

H19基因的单核苷酸多态性与猪生长性状的相关分析及其时空表达

本试验为了了解H19基因在猪骨骼肌生长发育过程中的作用,首先采用实时荧光定量PCR的技术检测了H19的组织分布以及在骨骼肌生长发育中的动态表达。然后通过混合池测序检测了H19外显子和内含子区的单核苷酸多态位点(SNP),利用质谱在大白猪群体中进行SNPs位点基因型鉴定,并进行标记性状关联分析。H19基因在大白猪的心、肝、脾、肺、肾、小肠、胃、腿肌、背肌中均有表达,且在骨骼肌(腿肌、背肌)和肾中高表达。在骨骼肌发育中,H19主要是在胚胎期和出生后40d之前有较高表达量,并且在胚胎期105d达到最大值。对7个SNPs位点进行相关性分析,结果显示,RS15位点与达100kg体重的校正日龄显著相关(P=0.046 2<0.05),RS20位点与100kg的校正眼肌面积显著相关(P=0.009 5<0.01)。RS15与RS16紧密连锁,其单倍型与校正背膘厚显著相关(P=0.049 8<0.05);RS17与RS18单倍型与达100kg的校正眼肌面积显著相关(P=0.037 1<0.05)。结果表明H19基因参与猪骨骼肌发育调控,是猪产肉性状的候选基因。

Role of long non-coding RNAs in gene regulation and oncogenesis

Objective This article aims to review recent studies on the biological characteristics of long non-coding RNAs （IncRNAs）, transcription regulation by IncRNAs, and the results of recent studies on the mechanism of action of IncRNAs in tumor development. Data sources The data cited in this review were mainly obtained from the articles listed in PubMed and HighWire that were published from January 2002 to June 2010. The search terms were ＂long non-coding RNA＂, ＂gene regulation＂, and ＂tumor＂. Study selection The mechanism of IncRNAs in gene expression regulation, and tumors concerned with IncRNAs and the role of IncRNAs in oncogenesis. Results IncRNAs play an important role in transcription control, and post-transcriptional controlling. IncRNAs are suppressing and promoting factors. regulation by controlling chromatin remodeling, transcriptional involved in many kinds of tumors and play key roles as both Conclusion IncRNAs could perfectly regulate the balance of gene expression system and play important roles in oncogenic cellular transformation.

Integrative Analysis Reveals Enhanced Regulatory Effects of Human Long Intergenic Non-Coding RNAs in Lung Adenocarcinoma

Although there is an accumulating appreciation of the key roles that long intergenic non-coding RNAs （lincRNAs） play in diverse cellular processes, our knowledge of how lincRNAs function in cancer remains sparse. Here, we present a comprehensive landscape of RNA-seq transcriptome profiles of lung adenocarcinomas and their paired normal counterparts to unravel gene regulation rules of lincRNAs. Consistent with previous findings of co-expression between neighboring protein-coding genes, lincRNAs were typically co-expressed with their neighboring genes, which was found in both cancerous and normal tissues. By building a mathematical model based on correlated gene expression, we distinguished an additional subset of lincRNAs termed ＂regulatory lincRNAs＂, representing their dominant roles in gene regulation. The number of regulatory lincRNAs was significantly higher in cancerous compared to normal tissues, and most of them positively regulated protein-coding genes in trans. Functional validation, using knockdown, determined that regulatory lincRNA, GASS, affected its predicted protein-coding targets. Moreover, we discovered hundreds of differentially expressed regulatory lincRNAs with inclusion of some cancer-associated lincRNAs. Our integrated analysis reveals enhanced regulatory effects of lincRNAs and provides a resource for the study of regulatory lincRNAs that play critical roles in lung adenocarcinoma.

Role of long non-coding RNAs in normal and malignant hematopoiesis

Long non-coding RNAs(lncRNAs)are defined as a class of nonprotein-coding transcripts greater than 200 nucleotides in length,which have diverse functions in development and diseases including hematopoiesis.Recent advances have revealed that lncRNAs regulate hematopoietic development at almost every stage,including differentiation of the myelocyte,lymphocyte,and erythrocyte.Abnormal regulation of the lncRNAs may block aspects of blood development,which can lead to different types of hematopoietic disorders.These findings highlight the role of lncRNAs as potential therapeutic tools in malignant hematopoiesis.In this review,we summarize recent progress in the study of functional lncRNAs associated with blood development,as well as dysregulated lncRNAs involved in diverse blood diseases by interacting with crucial susceptibility genes in different pathways.In addition,we discuss genome-wide studies on lncRNAs,which are helpful for genome screening and in-depth functional study of lncRNAs associated with blood development and disease.

Role of circulating long non-coding RNA for the improvement of the predictive ability of the CHA_(2)DS_(2)-VASc score in patients with atrial fibrillation

Background:The CHA_(2)DS_(2)-VASc score was initially applied to stratify stroke risk in patients with atrial fibrillation(AF)and was found to be effective in predicting all-cause mortality outcomes.To date,it is still unclear whether circulating long non-coding RNAs(lncRNAs)as emerging biomarkers,can improve the predictive power of the CHA_(2)DS_(2)-VASc score in stroke and all-cause mortality.Methods:Candidate lncRNAs were screened by searching the literature and analyzing previous RNA sequencing results.After preliminary verification in 29 patients with AF,the final selected lncRNAs were evaluated by Cox proportional hazards regression in 192 patients to determine whether their relative expression levels were associated with stroke and all-cause mortality.The c-statistic,net reclassification improvement(NRI),and integrated discrimination improvement of the patients were calculated to evaluate the discrimination and reclassification power for stroke and all-cause mortality when adding lncRNA expression levels to the CHA_(2)DS_(2)-VASc score model.Results:Five plasma lncRNAs associated with stroke and all-cause mortality in AF patients were selected in our screening process.Patients with elevated H19 levels were found to have a higher risk of stroke(hazard ratio[HR]3.264,95% confidence interval[CI]:1.364–7.813,P=0.008).Adding the H19 expression level to the CHA_(2)DS_(2)-VASc score significantly improved the discrimination and reclassification power of the CHA_(2)DS_(2)-VASc score for stroke in AF patients.In addition,the H19 level showed a marginally significant association with all-cause mortality(HR 2.263,95%CI:0.889–5.760,P=0.087),although it appeared to have no significant improvement for the CHA_(2)DS_(2)-VASc model for predicting all-cause mortality.Conclusions:Plasma expression of H19 was associated with stroke risk in AF patients and improved the discriminatory power of the CHA_(2)DS_(2)-VASc score.Therefore,lncRNA H19 served as an emerging non-invasive biomarker for stroke risk prediction in patients with AF.

The Messenger RNA and Long Non-coding RNA Expression Profiles in Ectopic and Eutopic Endometrium Provide Novel Insights into Endometriosis

Objective:To establish the messenger RNA(mRNA)and long non-coding RNA(lncRNA)expression profiles in ectopic and eutopic endometrium and provide novel insights into endometriosis.Methods:The mRNA and lncRNA expression profiles were tested using high-throughput sequencing technology in ectopic and eutopic endometrium with endometriosis and normal endometrium without endometriosis.The potential targeted lncRNAs were annotated by analyzing the correlation between lncRNA and mRNA expression to better understand the pathogenesis of endometriosis.Results:In ectopic compared with normal endometrium,a total of 2,188 mRNAs and 1,200 lncRNAs were differentially expressed with a fold-change(FC)≥2.5.In eutopic compared with normal endometrium,a total of 2,324 mRNAs and 695 lncRNAs were differentially expressed with an FC≥1.5.In ectopic compared with eutopic endometrium,a total of 2,223 mRNAs and 511 lncRNAs were differentially expressed with an FC≥2.Bioinformatic analysis indicated that the differentially expressed mRNAs were enriched in the biological processes and signaling pathways involved in endometriosis.In addition,we constructed a gene coexpression network based on the dysregulated lncRNAs in both ectopic endometrium and eutopic endometrium,combined with their coexpressed mRNAs to simulate the complex interactions.Conclusions:This study describes the first-to-integrate analysis of the differential expression profiles of mRNAs and lncRNAs,including analyses between ectopic and normal endometrium,eutopic and normal endometrium,and ectopic and eutopic endometrium,which provides new insights to investigate the pathogenesis of endometriosis and explore novel diagnostic biomarkers and therapeutic targets.

长链非编码RNA在甲状腺乳头状癌中的表达谱分析

研究发现长链非编码RNA（long noncoding RNA,lncRNA）在人类多种恶性肿瘤（如肝癌、肺癌、乳腺癌等）的发生和发展中发挥重要作用,但其在甲状腺肿瘤中的表达及作用机制的研究较少。本研究采用基因芯片检测甲状腺乳头状癌（papillary thyroid carcinoma,PTC）和甲状腺良性肿瘤组织中lncRNAs/m RNAs的表达,筛选PTC差异性表达的lncRNAs,