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