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miR-489-3p Inhibits Prostate Cancer Progression by Targeting DLX1

Authors Bai P, Li W, Wan Z, Xiao Y, Xiao W, Wang X, Wu Z, Zhang K, Wang Y, Chen B, Xing J, Wang T

Received 25 November 2019

Accepted for publication 31 March 2020

Published 23 April 2020 Volume 2020:12 Pages 2719—2729

DOI https://doi.org/10.2147/CMAR.S239796

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Seema Singh


Peide Bai,1 Wei Li,1 Zhenghua Wan,2 Yujuan Xiao,3 Wen Xiao,1 Xuegang Wang,1 Zhun Wu,1 Kaiyan Zhang,1 Yongfeng Wang,1 Bin Chen,1 Jinchun Xing,1 Tao Wang1

1The Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology Surgery, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen 361003, People’s Republic of China; 2Xiang’an Branch, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen 361101, People’s Republic of China; 3Department of Pediatrics, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen 361003, People’s Republic of China

Correspondence: Jinchun Xing; Tao Wang
The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, People’s Republic of China
Tel/Fax +86-592-2139814; +86-592-2137125
Email xmcua2007@sina.com; taowang@xmu.edu.cn

Purpose: Prostate cancer (PCa) is the third most common cancer in men and the second leading cause of cancer-related death in men. DLX1 belongs to the DLX homeobox family and exhibits antitumor activity in many kinds of tumors. MicroRNAs (miRNAs) play important roles in the progression of cancer. However, whether miRNAs affect the development of PCa by targeting DLX1 has not been determined. In this study, we aimed to investigate the role of miR-489-3p in the regulation of DLX1 expression and PCa progression and to provide a potential therapeutic target for PCa treatment.
Methods and Materials: The Cancer Genome Atlas database was used to analyze the divergent expression of DLX1 in carcinomas and adjacent normal tissues. The expression level of DLX1 in malignant and normal prostate cells was also measured using RT-qPCR and Western blotting. A dual-luciferase reporter assay was performed to determine whether miR-489-3p directly targets DLX1. We transfected 22Rv1 and DU145 cells with miR-489-3p mimics to overexpress miR-489-3p and then evaluated its effect on cellular function. MTT, EdU, colony formation and cell cycle assays were used to evaluate cell growth. JC-1 and ROS assays with flow cytometry were performed to indirectly analyze apoptosis. Transwell assays were conducted to investigate metastasis.
Results: The expression level of DLX1 was upregulated in both PCa tissues and cell lines. MiR-489-3p directly targeted DLX1 and downregulated its expression. Overexpression of miR-489-3p significantly suppressed cell growth. MiR-489-3p induced apoptosis through mitochondrial function impairment. Overexpression of miR-489-3p also inhibited cell migration and invasion. DLX1 overexpression reversed the above effects induced by miR-489-3p.
Conclusion: We identified the involvement of the miR-489-3p/DLX1 pathway in PCa for the first time. In this pathway, miR-489-3p acts as a tumor suppressor by negatively regulating the expression of DLX1. MiR-489-3p may be a potential therapeutic target for PCa treatment.

Keywords: prostate cancer, DLX1, miR-489-3p, growth, apoptosis, migration, invasion

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