The m6A transferase METTL3 regulates high glucose-induced proliferation and apoptosis of human lens epithelial cells through the lncRNA TUG1/KHSRP/p38MAPK signaling axis.

Diabetic cataract (DC) is one of the ocular complications in diabetic patients. This study aimed to investigate the mechanism of Methyltransferase-like 3 (METTL3)/Long non-coding RNA taurine-upregulated gene 1 (lncRNA TUG1)/KH-type splicing regulatory protein (KHSRP)/p38 mitogen-activated protein kinase (p38MAPK) signaling axis in DC progression. The expression of METTL3, TUG1, KHSRP, p38, and apoptosis-related proteins in tissues and cells were detected by RT-qPCR or Western blot. The m6A level was quantified using m6A colorimetric assay. RNA immunoprecipitation (RIP) assay verified the binding between RNA and protein. Proliferation and apoptosis of human lens epithelial cells (HLECs) were analyzed by CCK8 assay and flow cytometry. High glucose (HG) increased METTL3-mediated m6A methylation, which increased TUG1 expression. Knockdown of TUG1 increased HG-induced cell proliferation and decreased apoptosis. Knockdown of TUG1 decreased KHSRP expression, and RIP assays showed that TUG1 bound to KHSRP. Knockdown of KHSRP reversed the decrease in cell proliferation and increase in apoptosis caused by TUG1 expression. KHSRP affects the phosphorylation level of p38 and regulates cell proliferation and apoptosis through the p38MAPK pathway. This suggests that the m6A transferase METTL3 regulates DC proliferation and apoptosis through the lncRNA TUG1/KHSRP/p38MAPK signaling axis, providing a novel target for the treatment of DC.