LncRNA and mRNA interaction study based on transcriptome profiles reveals potential core genes in the pathogenesis of human thoracic aortic dissection

摘要

The aim of the present study was to determine the potential core genes in the pathogenesis of human thoracic aortic dissection (TAD) by analyzing microarray profiles of long non-coding (lnc)-RNAs between TAD and normal thoracic aorta (NTA). The differentially expressed lncRNA profiles of the aorta tissues between TAD patients (TAD group, n=6) and age-matched donors with aortic diseases (NTA group, n=6) were analyzed by lncRNAs microarray. Gene ontology (GO), pathway and network analyses were used to further investigate candidate lncRNAs and mRNAs. Differentially expressed lncRNAs and mRNAs were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In total, the present study identified 765 lncRNAs and 619 mRNAs with differential expression between TAD and NTA (fold change >2.0, P<0.01). GO analysis demonstrated that the differentially upregulated lncRNAs are associated with cell differentiation, homeostasis, cell growth and angiogenesis. Kyoto Encyclopedia of Gene and Genomes pathway analysis demonstrated that the differentially downregulated lncRNAs are mainly associated with arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy and dilated cardiomyopathy. To reduce the lncRNAs for further investigation and to enrich those potentially involved in TAD, a total of 16 candidate lncRNAs with a significant expression (fold change >4, P<0.01) were selected, that were associated with an annotated protein-coding gene through the GO term and scientific literatures. Then a set of significantly expressed lncRNAs [purinergic receptor P2X7 (P2RX7), hypoxia inducing factor (HIF)-1A-AS2, , RP11-69I8.3 and RP11-536K7.5) and the corresponding mRNAs (P2RX7, cyclin dependent kinase inhibitor 2B, HIF-1A, runt-related transcription factor 1, connective tissue growth factor and interleukin 2 receptor a chain] were confirmed using RT-qPCR. The present study revealed that the expression profiles of lncRNAs and mRNAs in aorta tissues from TAD were significantly altered. These results may provide important insights into the pathogenesis of TAD disease.