RBM15 drives the progression of lung adenocarcinoma by regulating N6-methyladenosine-mediated LDHA mRNA stability

Abstract

Abnormal N6-methyladenosine (m6A) methylation in RNA plays a pivotal role in the pathogenesis of many types of tumors by influencing mRNA metabolism, alternative splicing, translocation, stability and translation. However, the specific regulators and underlying mechanisms of m6A modification in the progression of lung adenocarcinoma are not well understood. In this study, we analyzed the RNA-seq transcriptome data downloaded from The Cancer Genome Atlas (TCGA) database, and identified "m6A writer" RNA binding motif protein 15 (RBM15) expression was significantly elevated in lung adenocarcinoma (LUAD) biopsies, and the higher RBM15 levels were correlated with the poorer overall survival (OS) of LUAD patients. Further study confirmed RBM15 was prominently expressed in LUAD tissues and cell lines. Moreover, silencing RBM15 in PC9 and H1299 cells reduced cell proliferation both in vitro and in vivo, while overexpression of RBM15 in A549 cells promoted cell growth. Mechanistically, lactate dehydrogenase A (LDHA) acted as a downstream target of RBM15. RBM15-mediated m6A modification of LDHA mRNA enhanced its stability to exert an oncogenic role in LUAD. Taken together, our findings suggest that the RBM15/LDHA axis might be a novel and promising therapeutic target for LUAD.

Keywords: LDHA; Lung adenocarcinoma; RBM15; m6A.