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.