N6-methyladenosine writer KIAA1429 modulates the proliferation/migration of endothelial cells for atherosclerosis

Abstract

Increasing evidence illustrates the important roles of N6-methyladenosine (m6A) in progression of atherosclerosis (AS). However, the connections between m6A modification and AS pathophysiological process are unknown. Here, this work investigated the expression profile of m6A methyltransferase KIAA1429 in AS pathology and explored its undergoing m6A-dependent molecular mechanism. Results indicated that KIAA1429 was remarkedly up-regulated in oxidative low-density lipoprotein (ox-LDL) treated human umbilical vein endothelial cells (HUVECs). KIAA1429 overexpression inhibited proliferation/migration in ox-LDL-administrated HUVECs, while, KIAA1429 knockdown repressed the proliferation and migration. Mechanistically, ROCK2 mRNA was post-transcriptionally upregulated by KIAA1429 in response to Actinomycin D administration through m6A modified site binding on ROCK2 mRNA. Collectively, our study demonstrates the functional regulation of KIAA1429 on ox-LDL-induced HUVECs via m6A/ROCK2 axis. These findings provide new insights for m6A-mediated epigenetics in AS.