AUTHOR=Mei Yu , Li Kai , Zhang Zhicheng , Li Mengmeng , Yang Hong , Wang Hui , Huang Xuemei , Li Xinyuan , Shi Shuhua , Yang Huanjie TITLE=miR-33b-3p Acts as a Tumor Suppressor by Targeting DOCK4 in Prostate Cancer JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.740452 DOI=10.3389/fonc.2021.740452 ISSN=2234-943X ABSTRACT=

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.