Mettl3-mediated transcriptome-wide m6A methylation induced by cigarette smoking in human bronchial epithelial cells.

Cigarette smoke exposure is a well-recognized causative factor for Chronic obstructive pulmonary disease (COPD), but the molecular mechanisms responsible for this effect need to be further investigated. An expanding number of studies suggest that m6A modification is involved in the progression of various diseases. Nevertheless, evidence on the regulatory function of m6A modification in human bronchial epithelial cells exposed to cigarette smoke is scarce. In this study, we investigated for the first time the effect of cigarette smoke exposure on contributing to high Mettl3 expression in HBE cells in vitro, an essential m6A writer. To investigate the pattern of m6A modification in HBE cells following cigarette smoke exposure, Mettl3 was down-regulated in HBE cells and a MeRIP-seq analysis revealed differences in m6A methylation between wild-type (WT) and Mettl3 knockdown HBE cells exposed to CSE. There were 1584 significantly hypomethylated genes engaged in multicellular organismal developments. We identified 200 differentially expressed genes with hypomethylated m6A peaks in conjunction with Mettl3 knockdown, among four candidate genes (NR1H4, TSPEAR, ACSBG1, and SLC5A5) that could be further explored in COPD. According to the research, cigarette smoke may control the behavior of human bronchial epithelial cells through m6A modification in COPD, providing a unique molecular mechanism.