RBM15 facilities lung adenocarcinoma cell progression by regulating RASSF8 stability through N6 Methyladenosine modification
Mingsheng Ma, Wei Wang, Li Li, Xiaoyan Wang, Qiubo Huang, Chen Zhou, Yunchao Huang, Guangqiang Zhao, Lianhua Ye
Abstract
• RBM15-mediated m6A modification facilitates the progression of lung adenocarcinoma. • RASSF8 was a downstream target of RBM15-mediated m6A modification. • RBM15 can increase the methylation enrichment of RASSF8. • RBM15/m6A/RASSF8 axis may be a novel target for the treatment of lung adenocarcinoma. Invasion and migration are the primary factors for mortality in lung adenocarcinoma (LUAD) patients. The precise role of RNA-binding motif protein15 (RBM15)-mediated m6A modification in LUAD is not yet fully clarified. This research aims to elucidate the mechanism of RBM15 in the invasion and migration of LUAD. Western blot and dot blot assay results showed that RBM15 and methylation levels of m6A were highly expressed in LUAD tissues. Overexpression of RBM15 by lentivirus transfection increased m6A levels and promoted the invasion, migration, and proliferation of A549 and H1734 cells. Knockdown of RBM15 by lentivirus transfection had opposite effects on m6A levels, invasion, migration, and proliferation of A549 and H1734 cells. The results of nude mouse proliferation models confirmed that RBM15 knockdown inhibited in vivo tumor proliferation . Sequencing and immunoprecipitation identified RASSF8 as an interacting protein of RBM15 involved in cell invasion and migration. RBM15-mediated m6A modification inhibited RASSF8 protein levels and increased LUAD cell invasion and migration. The rescue assays demonstrated that the regulation of RBM15 on LUAD cell invasion and migration was partially rescued by RASSF8. In conclusion, RBM15-mediated m6A modification inhibits the RASSF8 protein levels and increases cell invasion and migration. Thus, targeting the RBM15-m6A-RASSF8 axis may be a promising strategy for repressing LUAD cell invasion and migration.