METTL3 suppresses invasion of lung cancer via SH3BP5 m6A modification.

ABSTRACT

The metastasis of lung cancer poses a major clinical challenge, and m6A modification has been implicated in regulating the invasive capabilities of tumor cells. However, the mechanisms underlying m6A modification in lung cancer metastasis are not well understood. This study aims to explore the biological functions and molecular mechanisms of methyltransferase-like 3 (METTL3) in lung cancer. In this study, METTL3 were found to be downregulated in lung cancer tissues. Functionally, METTL3 inhibited the migration and invasion abilities of lung cancer cells in vitro. Furthermore, SH3 domain binding protein 5 (SH3BP5) was identified as a downstream target of METTL3. Overexpression of SH3BP5 suppressed the invasive capacity of lung cancer cells, and this regulation was m6A-dependent. Finally, we discovered that YTH N6-methyladenosine RNA binding protein F1 (YTHDF1) mediated stability is responsible for maintaining the m6A modification of SH3BP5 mRNA. Overall, our study provides insights into the critical role of METTL3-mediated m6A modification and m6A-dependent regulatory mechanisms in the progression of human lung cancer. We demonstrated that METTL3 regulates the mRNA stability of SH3BP5 in a YTHDF1-dependent manner, thereby impacting the invasive capacity of lung cancer cells.