Expression Pattern and Clinical Value of Key m6A RNA Modification Regulators in Abdominal Aortic Aneurysm

Abstract

Tan Li,1 Tianlong Wang,2 Jingjing Jing,3,4 Liping Sun3,4 1Department of Cardiovascular Ultrasound, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 2The First Clinical College of China Medical University, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 3Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 4Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Liping SunTumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, No. 155 NanjingBei Street, Heping District, Shenyang, Liaoning Province, 110001, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: Aberrant expression of N6-methyladenosine (m6A) RNA modification regulators plays a critical role in a variety of human diseases. However, their implication in abdominal aortic aneurysm (AAA) remains largely unknown. Herein, we sought to explore the general expression pattern and potential functions of m6A regulators in AAA.Methods: We analyzed gene expression data of m6A regulators in human AAA and normal tissues from public GEO database. The R package and other tools such as m6A2Target database, Gene ontology (GO) functional and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses, gene set variation analysis (GSVA), Search Tool for the Retrieval of Interacting Genes (STRING), starBase, miRDB and Cytoscape software were applied for bioinformatics analysis to investigate the downstream molecular mechanisms and upstream regulatory mechanisms for distinctly expressed regulators. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were performed to validate the expression of key m6A regulators in our collected human AAA specimens.Results: We found that METTL14 and HNRNPC were the downregulated m6A regulators, and RBM15B was the upregulated methylation transferase in human AAA. The modified genes were primarily enriched in RNA catabolic process, regulation of translation, focal adhesion, transcription coregulator activity, ribosome, RNA transport, cell cycle, et al. METTL14, HNRNPC and RBM15B levels were correlated with the immune infiltration degree of Tcm, macrophages, mast cells, Tgd and NK CD56bright cells. A total of 154 and 76 target genes of three regulators were separately involved in body metabolism and autophagy in AAA disease, and their interactive relationships and hub genes were identified. The lncRNA-miRNA-mRNA interaction regulatory networks were also constructed for METTL14, HNRNPC and RBM15B. Based on our clinical tissue and serum samples, METTL14 exhibited lower expression levels in AAA and its rupture type, and low METTL14 expression was associated with high levels of WBC and CRP (all P < 0.05).Conclusion: Our study presents an overview of the expression pattern and functional significance of m6A regulators in human AAA. Our findings will provide a valuable resource that may guide both mechanistic and therapeutic analyses about the role of key m6A regulators in AAA.Keywords: abdominal aortic aneurysm, gene expression, m6A modification

Keywords

• abdominal aortic aneurysm
• gene expression
• m6a modification