miR-28-5p acts as a tumor suppressor in renal cell carcinoma for multiple antitumor effects by targeting RAP1B

• DOI: 10.18632/oncotarget.12516
• Publication Date: 2016-10-07T21:03:00Z
• Authors: Cheng Wang; Caiyun Wu; Qi Yang; Meng Ding; Jinsha Zhong; Chen-Yu Zhang; Jingping Ge; Junjun Wang; Chunni Zhang
• Keywords: Male; 0301 basic medicine; 0303 health sciences; MAP Kinase Signaling System; Kidney Neoplasms; 3. Good health; Gene Expression Regulation, Neoplastic; Disease Models, Animal; Mice; MicroRNAs; 03 medical and health sciences; rap GTP-Binding Proteins; Cell Movement; Cell Line, Tumor; Animals; Heterografts; Humans; Genes, Tumor Suppressor; RNA Interference; Phosphorylation; Carcinoma, Renal Cell; Research Paper; Cell Proliferation

The incidence and mortality rate of renal cell carcinoma (RCC) have been significantly increasing; however, the mechanisms involved in RCC development and progression are unclear. In this study, we found that miR-28-5p was decreased in RCC tumor specimens and several renal carcinoma cell lines. By using a combination of luciferase reporter assays and western blotting, we identified RAP1B, a Ras-related small GTP-binding oncoprotein implicated in a variety of tumors, as a direct target of miR-28-5p in RCC. The RAP1B protein level was increased in RCC tumor specimens and renal carcinoma cell lines, and this was inversely correlated with miR-28-5p expression. In vitro gain-of-function and loss-of-function studies in human renal carcinoma cell lines, demonstrated that miR-28-5p suppressed cell proliferation and migration by directly inhibiting RAP1B, and this effect was reversed by co-transfection with RAP1B. In addition, the stable overexpression of miR-28-5p inhibited tumor cell proliferation in vivo. This newly identified miR-28-5p/RAP1B axis provides a novel mechanism for the pathogenesis of RCC, and molecules in this axis may serve as potential biomarkers and therapeutic targets for RCC.