Oncotarget

Research Papers:

miR-93-3p inhibition suppresses clear cell renal cell carcinoma proliferation, metastasis and invasion

Lu Wang, Guang Yang, Xiangwei Zhu, Ziqi Wang, Hongzhi Wang, Yang Bai, Pengcheng Sun, Li Peng, Wei Wei, Guang Chen, Guangbin Li, Andrey A. Zamyatnin Jr, Peter V. Glybochko and Wanhai Xu _

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Oncotarget. 2017; 8:82824-82834. https://doi.org/10.18632/oncotarget.20458

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Abstract

Lu Wang1,*, Guang Yang2,*, Xiangwei Zhu1, Ziqi Wang1, Hongzhi Wang1, Yang Bai1, Pengcheng Sun1, Li Peng1, Wei Wei1, Guang Chen1, Guangbin Li1, Andrey A. Zamyatnin Jr3,4, Peter V. Glybochko3,4 and Wanhai Xu1

1Department of Urology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang Province, P.R. China

2Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, P.R. China

3Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow, Russia

4A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia

*These authors have contributed equally to this work

Correspondence to:

Wanhai Xu, email: [email protected]

Keywords: ccRCC, miR-93-3p, PEDF, apoptosis, migration

Received: January 02, 2017     Accepted: June 29, 2017     Published: August 24, 2017

ABSTRACT

miRNA dysregulation is associated with many human diseases, including cancer. This study explored the effects of miR-93-3p on clear cell renal cell carcinoma (ccRCC). We found that miR-93-3p is upregulated an average of 38-fold in 138 ccRCC specimens compared to matched normal kidney tissues, which correlated with poor patient outcome. miR-93-3p inhibition reduced ccRCC cell growth, invasion, and migration in vitro and in a mouse xenograft model. A search of the TargetScan, miRanda, and PicTar databases revealed that miR-93-3p is predicted to regulate pigment epithelium-derived factor (PEDF). A direct PEDF-miR-93-3p interaction was confirmed via dual-luciferase reporter assays. Like miR-93-3p inhibition, PEDF overexpression induced cell apoptosis and inhibited migration and invasion. Additionally, co-transfection with PEDF siRNA reversed the effects of miR-93-3p inhibition in ccRCC cells. Thus, miR-93-3p is a likely ccRCC oncogene that acts by regulating PEDF. These results suggest that miR-93-3p may predict ccRCC patient clinical outcome and serve as a novel anti-ccRCC therapeutic target.


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