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

Background : N6-methyladenosine (m ⁶ A) 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 (m ⁶ A) modification and the expressions of the m ⁶ A 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 m ⁶ A 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 m ⁶ A 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 m ⁶ A level and mRNA abundance in AD cases compared with the controls. We observed the same m ⁶ A-level changes in 14 out of the 16 selected m ⁶ A methylated transcripts in the independent sample. Conclusions : This study identified m ⁶ A changes in critical AD susceptibility genes. The identified m ⁶ A modification may play a role in critical AD-related pathways, thereby regulating the pathogenesis of AD.