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

Author:

Chen Lihao1ORCID,Hu Yu1,Zhang Min1,Liu Lihao1,Ma Jing1,Xu Zhuohong1,Zhang Jiaan1,Gu Heng1,Chen Kun1

Affiliation:

1. Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing China

Abstract

AbstractExposure 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.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Jiangsu Province

Chinese Academy of Medical Sciences Initiative for Innovative Medicine

Publisher

Wiley

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