LncRNA Expression Profile Of Human Thoracic Aortic Dissection By High-Throughput Sequencing

BackgroundAcute thoracic aortic dissection（TAD）is one of the most lethal cardiovascular diseases.The mechanism of TAD may still occur.Non-coding RNAs are rapidly emerging as crucial regulatory molecules in the development of aortic disease.Long non-coding RNAs（lncRNAs）are involved in various biological processes via the dysregulation of target gene expression.They play important roles in pathophysiological changes of vascular SMC and ECM.Various lncRNAs,such as ANRIL,SENCR,LncRNA HIF1-AS 1,and lincRNA-p21,are involved in the regulation of human vascular SMC proliferation,contraction,migration,and apoptosis.The lncRNA HAS2-AS1 is involved in ECM remodeling via the regulation of HAS2 transcription in vascular SMC.Generally,lncRNA research related to human TAD has focused on their functions in individual cells.To date,no study has investigated the lncRNA expression profile in TAD tissues,particularly in human TAD tissues.In addition,previous studies have mainly used microarray technology,which cannot be used for whole-transcriptome analyses.Owing to its ability to be used for whole transcriptome analyses,high-throughput sequencing（HTS）technology is more suitable to characterize the genetic basis of diseases compared with microarrays.Therefore,we used HTS to investigate the lncRNA expression profile in human TAD tissues,and further applied a series of bioinformatics analyses to predict the functions of these lncRNAs.Objectives1.In this study,we investigated the lncRNAs expression profile in three human TAD and three normal aortic tissues（NA）with High-throughput sequencing.2.We performed various bioinformatics analyses for predicting the roles of aberrantly expressed lncRNAs in TAD.Methods1.Human TAD（n=3）and normal aortic tissues（NA）（n=3）were examined by high-throughput sequencing.2.Bioinformatics analyses were performed to predict the roles of aberrantly expressed lncRNAs.3.Quantitative real-time polymerase chain reaction（qRT-PCR）was applied to validate the results.Results1.A total of 269 lncRNAs（159 up-regulated and 110 down-regulated）and 2 255 mRNAs（1 294 up-regulated and 961 down-regulated）were aberrantly expressed in human TAD（fold-change>2.0,P<0.05）.QRT-PCR results for five dysregulated genes were consistent with HTS data.2.A lncRNA-mRNA coexpression analysis showed positive correlations between a up-regulated lncRNA（ENSG00000269936）and adjacent up-regulated mRNA（MAP2K6,R=0.940,P<0.01）,and between the down-regulated lncRNA₁421 and its down-regulated mRNAs（FBLN5,R=0.950,P<0.01;ACTA2,R=0.96,P<0.01;TIMP3,R=0.96,P<0.01）.3.The lnCRNA-miRNA-mRNA network indicated that the up-regulated IncRNA XIST and p21 had similar sequences targeted by has-miR-17-5p,and qRT-PCR results showed that lncRNA XIST and p21 were expressed at higher levels and has-miR-17-5p was expressed at lower levels in TAD than in NA.4.The predicted binding motifs of three up-regulated lncRNAs（ENSG00000248508,ENSG00000226530,and EG00000259719）were correlated with up-regulated RUNX1（R=0.982,P<0.001;R=0.967,P<0.01;R=0.960,P<0.01,respectively）.ConclusionOur study revealed a set of dysregulated lncRNAs and predicted multiple potential functions in human TAD.These findings suggest that lncRNAs are novel therapeutic targets for human TAD.