METTL14 affects UVB-induced human dermal fibroblasts photoaging via miR-100-3p biogenesis in an m6A-dependent manner

Abstract

Exposure to ultraviolet radiation can lead to skin photoaging, which increases the risk of skin tumors. This study aims to investigate how microRNA m⁶A modification contributes to skin photoaging. This study found that skin fibroblasts exposed to a single UVB dose of 30 mJ/cm² exhibited characteristics of photoaging. The m⁶A level of total RNA decreased in photoaged cells with a down-regulated level of METTL14, and overexpression of METTL14 displayed a photoprotective function. Moreover, miR-100-3p was a downstream target of METTL14. And METTL14 could affect pri-miR-100 processing to mature miR-100-3p in an m⁶A-dependent manner via DGCR8. Furthermore, miR-100-3p targeted at 3' end untranslated region of ERRFI1 mRNA with an inhibitory effect on translation. Additionally, photoprotective effects of overexpression of METTL14 were reversed by miR-100-3p inhibitor or overexpression of ERRFI1. In UVB-induced photoaging of human skin fibroblasts, METTL14-dependent m⁶A can regulate miR-100-3p maturation via DGCR8 and affect skin fibroblasts photoaging through miR-100-3p/ERRFI1 axis.

Keywords: ERRFI1; METTL14; human dermal fibroblasts photoaging; m6A modification; miR‐100‐3p.