The hepatic microenvironment promotes lung adenocarcinoma cell proliferation, metastasis, and epithelial–mesenchymal transition via METTL3-mediated N6-methyladenosine modification of YAP1

The inflammatory microenvironment plays an important role in the onset and progression of lung adenocarcinoma (LUAD), and the liver is a suitable site of metastasis for LUAD cells. However, whether the inflammatory microenvironment of the liver is conducive to the proliferation, invasion, and metastasis of LUAD cells remains unclear. In this study, we confirmed that the hepatic inflammatory microenvironment stimulated by IL-6 promoted the proliferation, migration, invasion, and epithelial–mesenchymal transition of LUAD cells, increased the m6A methylation of total RNA, and transcriptionally activated METTL3 expression. Additionally, METTL3 activated the YAP1/TEAD signaling pathway by increasing the m6A modification and expression of YAP1 mRNA. These results indicate that the hepatic inflammatory microenvironment plays a role in regulating the biological functions of LUAD cells. Further, our study identifies a molecular mechanism that may provide a new strategy for the early diagnosis, treatment, and prognosis of liver metastasis in LUAD patients.