LncRNA Expression Profile of Human Thoracic Aortic Dissection by High-Throughput Sequencing

In this study, the long non-coding RNA (lncRNA) expression profile in human thoracic aortic dissection (TAD), a highly lethal cardiovascular disease, was investigated. Human TAD (n=3) and normal aortic tissues (NA) (n=3) were examined by high-throughput sequencing. Bioinformatics analyses were performed to predict the roles of aberrantly expressed lncRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the results. 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>1.5, P<0.05). QRT-PCR results of five dysregulated genes were consistent with HTS data. A lncRNA-mRNA coexpression analysis showed positive correlations between the up-regulated lncRNA (ENSG00000269936) and its adjacent up-regulated mRNA (MAP2K6, R=0.940, P<0.01), and between the down-regulated lncRNA_1421 and its down-regulated mRNAs (FBLN5, R=0.950, P<0.01; ACTA2, R=0.96, P<0.01; TIMP3, R=0.96, P<0.05). The lncRNA-miRNA-mRNA network indicated that the up-regulated lncRNA XIST and p21 had similar sequences targeted by has-miR-17-5p. The results of luciferase assay and fluorescence immuno-cytochemistry were consistent with that. And qRT-PCR results showed that lncRNA XIST and p21 were expressed at a higher level and has-miR-17-5p was expressed at a lower level in TAD than in NA. 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). Our study revealed a set of dysregulated lncRNAs and predicted their multiple potential functions in human TAD. These findings suggest that lncRNAs are novel potential therapeutic targets for human TAD. Aortic specimens were collected from three type A TAD patients undergoing aortic replacement in the intimal tear position at the hospital. Normal thoracic aortas (NA) were obtained from three age- and gender-matched organ donors without aortic diseases.