Transcriptome-wide identification of N6-methyladenosine modifications for aortic dissection

Abstract Background: N6-methyladenosine (m6A) plays important roles in many biological processes such as gene expression control and may have functional roles in aortic dissection (AD). The aim of this study was to identify N6-methyladenosine (m6A) modification and the expressions of the m6A regulatory genes related to AD. Methods: Aortic tissue samples were obtained from AD and controls and MeRIP-seq and RNA-seq experiments were performed to detect m6A methylation and mRNA expression profiles, respectively. The differentially RNA methylation peaks were validated by MeRIP-PCR in AD cases and controls. Results: Compared with the control samples, 3,318 up methylated and 1,573 down methylated coding genes in AD were detected. These genes were mainly enriched in focal adhesion, ECM-receptor interaction and regulating the transcription such as splicing. Significant differentially methylated m6A sites in some well-known susceptibility genes for AD were identified, including FBN1, TGFB1, TGFBR1/2, LOXL3, COL3A1, SMAD3, VEGFA and MAPK1/3. A total of 651 differentially expressed genes, including 594 protein-coding genes (96 upregulated and 498 downregulated), and 57 lncRNAs (20 upregulated and37 downregulated) were identified. Integrated analysis of the data from MeRIP-seq and RNA-Seq identified 74 genes that changed significantly in both m6A level and mRNA abundance in AD cases compared with the controls. We observed the same m6A-level changes in 14 out of the 16 selected m6A methylated transcripts in the independent sample. Conclusions: This study identified m6A changes in critical AD susceptibility genes. The identified m6A modification may play a role in critical AD-related pathways, thereby regulating the pathogenesis of AD.