Methyltransferase-like 14 silencing relieves the development of atherosclerosis via mA modification of p65 mRNA.

To explore the METTL14-dependent mA modification mechanism involved in the development of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) and the HUVEC cell line were used to establish an atherosclerosis cell model in vitro, and mice fed a high-fat diet were used as the animal model. Cell viability and apoptosis were assessed using MTT assays and flow cytometry. The status of mA in HUVECs was examined using MeRIP-qPCR. Oil Red O staining was used to evaluate the lesions or plaques on aortas separated from the target mice. METTL14 and METTL3 were upregulated in HUVECs after ox-LDL treatment. After transfection with si-METTL14, the bcl-2 expression level and the viability of ox-LDL-incubated cells increased, whereas the apoptosis rate and the expressions of Bax and cleaved caspase-3 decreased. However, the effect of METTL14 knockdown was reversed by p65 overexpression. After METTL14 knockdown, there was a decrease in the total mA content in HUVECs, mA modification, and p65 expression. The plaques and lesion areas on the high-fat diet mouse aortas were smaller after METTL14 silencing. METTL14 reduced cell viability and promoted apoptosis of HUVECs, which were both induced by ox-LDL via mA modification of p65. Knocking down METTL14 could inhibit the development of atherosclerosis in high-fat diet-treated mice.