Open Access

ARTICLE

MicroRNA-940 Targets INPP4A or GSK3β and Activates the Wnt/β-Catenin Pathway to Regulate the Malignant Behavior of Bladder Cancer Cells

Rong Wang, Yunfeng Wu, Weihua Huang, Weijun Chen

Department of Urology, The Jintan Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, P.R. China

Oncology Research 2018, 26(1), 145-155. https://doi.org/10.3727/096504017X14902261600566

Abstract

In this report, we aimed to explore the role and regulatory mechanism of microRNA-940 (miR-940) in bladder cancer development. The expressions of miR-940 in bladder cancer tissues and cells were measured. miR-940 mimics, miR-940 inhibitor small interference RNA against INPP4A (si-INPP4A), and GSK3b (si-GSK3b) and their corresponding controls were then transfected into cells. We investigated the effects of miR-940, INPP4A, or GSK3b on cell proliferation, migration, invasion, and apoptosis. Additionally, target prediction and luciferase reporter assays were performed to investigate the targets of miR-940. The regulatory relationship between miR-940 and the Wnt/β-catenin pathway was also investigated. miR-940 was upregulated in bladder cancer tissues and cells. Overexpression of miR-940 significantly increased bladder cancer cell proliferation, promoted migration and invasion, and inhibited cell apoptosis. INPP4A and GSK3b were the direct targets of miR-940, and knockdown of INPP4A or GSK3b significantly increased cancer cell proliferation, migration, and invasion and inhibited cell apoptosis. After miR-940 overexpression, the protein expression levels of c-Myc, cyclin D1, and β-catenin were significantly increased, and the expression levels of p27 and p-β-catenin were markedly decreased. The opposite effects were obtained after suppression of miR-940. XAV939, a tankyrase 1 inhibitor that could inhibit Wnt/β-catenin signaling, significantly reversed the effects of miR-940 overexpression on cell migration and invasion. Our results indicate that overexpression of miR-940 may promote bladder cancer cell proliferation, migration, and invasion and inhibit cell apoptosis via targeting INPP4A or GSK3b and activating the Wnt/β-catenin pathway. Our findings imply the key roles of suppressing miRNA-940 in the therapy of bladder cancer.

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