TGF-β Regulates m⁶A RNA Methylation after PM_2.5 Exposure

Abstract

PM2.5 exposure leads to a variety of respiratory diseases, including pulmonary fibrosis, metastatic lung cancer, etc. Exposure to PM2.5 results in the alteration of epigenetic modification. M6A RNA methylation is an essential epigenetic modification that regulates gene expression at the post-transcriptional level. Our previous study found that PM2.5 exposure up-regulated m6A RNA methylation and TGF-β expression level in the lung, but the mechanisms and pathways of PM2.5 regulation of m6A RNA methylation are still unclear. Moreover, a previous study reported that the TGF-β signal pathway could regulate m6A RNA methylation. Based on this evidence, we investigate the role of the TGF-β signaling pathway in PM2.5-induced m6A RNA methylation with the A549 cell line. Our results showed that PM2.5 could induce upregulation of m6A RNA methylation, accompanied by increased expression of TGF-β, Smad3, methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14). Furthermore, these alterations induced by PM2.5 exposure could be reversed by treatment with TGF-β inhibitor. Therefore, we speculated that the TGF-β signal pathway plays an indispensable role in regulating m6A RNA methylation after PM2.5 exposure. Our study demonstrates that PM2.5 exposure influences m6A RNA methylation by inducing the alteration of the TGF-β signal pathway, which could be an essential mechanism for lung-related diseases induced by PM2.5 exposure.

Keywords

• PM_2.5
• m⁶A
• RNA methyltransferase
• TGF-β
• A549