miR-33b-3p Acts as a Tumor Suppressor by Targeting DOCK4 in Prostate Cancer

Frontiers in Oncology

Zhicheng Zhang¹  Hong Yang¹  Hui Wang²  Xinyuan Li²  Yu Mei²  Xuemei Huang²  Mengmeng Li²  Kai Li²  Shuhua Shi²  Huanjie Yang² 

[1] Fourth Affiliated Hospital of Harbin Medical University, Harbin, China;School of Life Science and Technology, Harbin Institute of Technology, Harbin, China;

关键词: miR-33b-3p;    DOCK4;    metastasis;    prostate cancer;    proteasome inhibitor;   

DOI  :  10.3389/fonc.2021.740452

来源: DOAJ

【 摘 要 】

Despite that androgen-deprivation therapy results in long-lasting responses, the disease inevitably progresses to metastatic castration-resistant prostate cancer. In this study, we identified miR-33b-3p as a tumor suppressor in prostate cancer. miR-33b-3p was significantly reduced in prostate cancer tissues, and the low expression of miR-33b-3p was correlated with poor overall survival of prostate cancer patients. Overexpression of miR-33b-3p inhibited both migration and invasion of highly metastatic prostate cancer cells whereas inhibition of miR-33b-3p promoted those processes in lowly metastatic cells. The in vivo results demonstrate that miR-33b-3p suppresses metastasis of tail vein inoculated prostate cancer cells to lung and lymph nodes in mice. DOCK4 was validated as the direct target of miR-33b-3p. miR-33b-3p decreased the expression of DOCK4 and restoration of DOCK4 could rescue miR-33b-3p inhibition on cell migration and invasion. Moreover, downregulation of miR-33b-3p was induced by bortezomib, the clinically used proteasome inhibitor, and overexpression of miR-33b-3p enhanced the insufficient inhibition of bortezomib on migration and invasion as well as metastasis of prostate cancer cells. In summary, our findings demonstrate that miR-33b-3p suppresses metastasis by targeting DOCK4 in prostate cancer. Our results suggest that enhancing miR-33b-3p expression may provide a promising therapeutic strategy for overcoming that proteasome inhibitor’s poor efficacy against metastatic prostate cancer.

【 授权许可】

Unknown