Insights into the mechanism of METTL3-mediated m6A methylation in silicon dust-induced epithelial-mesenchymal transition.

Abstract

Silicosis is an occupational lung disease caused by long-term inhalation of silica dust. Its characteristic pathological manifestation is progressive pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) plays an important role in the occurrence and development of silicosis fibrosis, and N6-methyladenosine (m6A), as an important form of RNA modification, is closely related to the expression and regulation of multiple genes in the process of fibrosis. In the present study, we demonstrated that m6A modification significantly increases during silica-induced EMT. Silencing Methyltransferase Like 3 (METTL3) to reduce m6A modification levels inhibited the EMT process, suggesting that METTL3-mediated m6A modification could be an effective strategy for intervening in pulmonary fibrosis. Subsequently, through RNA sequencing, protein-protein interaction network analysis, and Methylated RNA Immunoprecipitation-RT-qPCR, we identified c-Myc as a downstream target of METTL3. In summary, our findings illuminate the relationship between m6A modification, METTL3, and the progression of silicosis, particularly through the EMT process. These results suggest that targeting METTL3 could be a promising therapeutic approach for modulating m6A levels and intervening in the progression of silicosis.