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

PM_2.5 exposure leads to a variety of respiratory diseases, including pulmonary fibrosis, metastatic lung cancer, etc. Exposure to PM_2.5 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 PM_2.5 exposure up-regulated m⁶A RNA methylation and TGF-β expression level in the lung, but the mechanisms and pathways of PM_2.5 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 PM_2.5-induced m⁶A RNA methylation with the A549 cell line. Our results showed that PM_2.5 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 PM_2.5 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 PM_2.5 exposure. Our study demonstrates that PM_2.5 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 PM_2.5 exposure.