N6-methyladenosine (m6A) writer METTL3 accelerates the apoptosis of vascular endothelial cells in high glucose

Abstract

Abstract Recent studies have shown that N6-methyladenosine (m6A) methylation, one of the most prevalent epigenetic modifications, is involved in the diabetes mellitus. However, whether m6A plays roles in diabetic vascular endothelium injury is still elusive. Present research aimed to investigate the regulation and mechanism of m6A on vascular endothelium injury. Upregulation of METTL3 was observed in the high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs), followed by upregulation of m6A methylation level. Functionally, METTL3 silencing repressed the apoptosis and recovered the proliferation of HUVECs disposed by HG. Moreover, HG exposure upregulated the expression of suppressor of cytokine signalling 3 (SOCS3). Mechanistically, METTL3 targeted the m6A modified site on SOCS3 genomic, which positively regulated the mRNA stability of SOCS3 mRNA. In conclusion, METTL3 silencing attenuated the HG-induced vascular endothelium cell injury via promoting SOCS3 expression. Our research expands the understanding of m6A on vasculopathy in diabetes mellitus and provides a potential strategy for the protection of vascular endothelial injury.