Oncotarget

Research Papers:

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

Dong-Hua Gu, Jia-Hui Mao, Xiao-Dong Pan, Hua Zhu, Xinfeng Chen, Bing Zheng and Yuxi Shan _

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Oncotarget. 2017; 8:26334-26343. https://doi.org/10.18632/oncotarget.15463

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Abstract

Dong-Hua Gu1,*, Jia-Hui Mao3,*, Xiao-Dong Pan1,2,*, Hua Zhu2, Xinfeng Chen2, Bing Zheng2, Yuxi Shan1

1The Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China

2The Department of Urology, The Second Affiliated Hospital of Nantong University, Nantong, China

3Department of Pathophysiology, Nantong University School of Medicine, Nantong, China

*These authors contributed equally to this work

Correspondence to:

Bing Zheng, email: bingzhengnantong@163.com

Yuxi Shan, email: drshanyuxisd@163.com

Keywords: renal cell carcinoma (RCC), Grb2-associated binding 2 (Gab2), microRNA-302c-3p, Akt and cell proliferation

Received: January 10, 2017     Accepted: February 02, 2017     Published: February 17, 2017

ABSTRACT

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.


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