microRNA-302c-3p inhibits renal cell carcinoma cell proliferation by targeting Grb2-associated binding 2 (Gab2)

• Published in: Oncotarget 2017-04, Vol.8 (16), p.26334-26343
• Main Authors: Gu, Dong-Hua, Mao, Jia-Hui, Pan, Xiao-Dong, Zhu, Hua, Chen, Xinfeng, Zheng, Bing, Shan, Yuxi
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - pathology; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Gene Silencing; Humans; Kidney Neoplasms - genetics; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; MicroRNAs - genetics; Proto-Oncogene Proteins c-akt - metabolism; Research Paper; RNA Interference; RNA, Small Interfering - genetics
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.15463

The expression and biological function of Grb2-associated binding 2 (Gab2) in renal cell carcinoma (RCC) cells was tested here. We showed that Gab2 expression was significantly elevated in human RCC tissues and RCC cells. It was correlated with over-activation of Akt and downregulation of microRNA-302c-3p ("miR-302c-3p"), a putative Gab2-targeting microRNA. Knockdown of Gab2 inhibited Akt activation and 786-O RCC cell proliferation. Reversely, forced over-expression of Gab2 led to Akt hyper-activation to facilitate 786-O cell proliferation. Exogenous expression of miR-302c caused Gab2 downregulation, Akt inhibition and 786-O cell proliferation inhibition. On the other hand, miR-302c-3p depletion by expressing its anti-sense ("antagomiR-302c") led to Gab2 upregulation, Akt activation and increased 786-O cell proliferation. Significantly, miR-302c-3p failed to affect the proliferation of 786-O cells with shRNA-depleted Gab2. Together, we suggest that miR-302c-3p depletion in human RCC cells leads to Gab2 over-expression, Akt hyper-activation and cell proliferation.