Oncotarget

Research Papers:

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

Cheng Wang, Caiyun Wu, Qi Yang, Meng Ding, Jinsha Zhong, Chen-Yu Zhang, Jingping Ge, Junjun Wang and Chunni Zhang _

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Oncotarget. 2016; 7:73888-73902. https://doi.org/10.18632/oncotarget.12516

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Abstract

Cheng Wang1,2,*, Caiyun Wu1,*, Qi Yang1,*, Meng Ding1,2, Jinsha Zhong1, Chen-Yu Zhang2, Jingping Ge3, Junjun Wang1, Chunni Zhang1,2

1Department of Clinical Laboratory, Jinling Hospital, State Key Laboratory of Analytical Chemistry for Life Science, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing 210002, China

2State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing 210023, China

3Department of Urology, Jinling Hospital, Nanjing University School of Medicine, Nanjing University, Nanjing 210002, China

*These authors contributed equally to this work

Correspondence to:

Chunni Zhang, email: [email protected]

Junjun Wang, email: [email protected]

Jingping Ge, email: [email protected]

Keywords: renal cell carcinoma, miR-28-5p, RAP1B, proliferation, migration

Received: December 02, 2015     Accepted: October 01, 2016     Published: October 07, 2016

ABSTRACT

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.


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