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; Wanhai Xu

doi:10.18632/oncotarget.20458

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

Oncotarget. 2017 Aug 24;8(47):82824-82834. doi: 10.18632/oncotarget.20458. eCollection 2017 Oct 10.

Authors

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 Jr^{3

4}, Peter V Glybochko^{3

4}, Wanhai Xu¹

Affiliations

¹ Department of Urology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang Province, P.R. China.
² Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, P.R. China.
³ Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow, Russia.
⁴ A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.

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.

Keywords: PEDF; apoptosis; ccRCC; miR-93-3p; migration.