Down regulation of RBM10 promotes proliferation and metastasis via miR-224-5p/RBM10/p53 feedback loop in lung adenocarcinoma

Abstract

RNA-binding motif protein 10 (RBM10) has a tumor suppressor role in multiple cancers. Combining Oncomine database results with tissue samples, Western blot analysis showed that RBM10 was significantly lower in lung adenocarcinoma (LUAD) than in adjacent normal tissues. Moreover, KM analysis revealed that the group with higher RBM10 expression in LUAD correlated with better overall survival (OS). Luciferase reporter assay revealed that an important tumor-promotive miRNA, miR-224-5p, was directly bound to the 3′UTR of RBM10, resulting in inhibition of RBM10 expression, and promoted LUAD progression both in vitro and in vivo. Mechanistically, we found that miR-224-5p directly targeted RBM10 to inhibit p53 expression during LUAD progression. Meanwhile, p53 affected RBM10 expression through p53/miR-224-5p axis. Our study identified RBM10 as a key tumor suppressor in the proliferation and metastasis of LUAD. The findings provide a novel mechanism involving a feedback loop of miR-224-5p/RBM10/p53 regulated tumor progression in LUAD, which may help with the design of more effective LUAD treatments.

Keywords

• Lung adenocarcinoma
• p53
• miR-224-5p
• RBM10