Silencing of PSMC2 inhibits development and metastasis of prostate cancer through regulating proliferation, apoptosis and migration

Qingke Chen,Lingmin Fu,Jieping Hu,Guanghua Guo,An Xie

doi:10.1186/s12935-021-01934-8

Abstract

BackgroundProstate cancer is the most common malignant tumor of male genitourinary system, molecular mechanism of which is still not clear. PSMC2 (proteasome 26S subunit ATPase 2) is a key member of the 19S regulatory subunit of 26S proteasome, whose relationship with prostate cancer is rarely studied.MethodsHere, expression of PSMC2 in tumor tissues or cells of prostate cancer was detected by qPCR, western blotting and immunohistochemical analysis. The effects of PSMC2 knockdown on cell proliferation, colony formation, cell migration, cell cycle and apoptosis were assessed by Celigo cell counting assay, colony formation assay, wound-healing assay, Transwell assay and flow cytometry, respectively. The influence of PSMC2 knockdown on tumor growth in vivo was evaluated by mice xenograft models.ResultsThe results demonstrated that PSMC2 was upregulated in tumor tissues of prostate cancer and its high expression was significantly associated with advanced Gleason grade and higher Gleason score. Knockdown of PSMC2 could inhibited cell proliferation, colony formation and cell migration of prostate cancer cells, while promoting cell apoptosis and cell cycle arrest. The suppression of tumor growth in vivo by PSMC2 knockdown was also showed by using mice xenograft models. Moreover, the regulation of prostate cancer by PSMC2 may be mediated by Akt/Cyclin D1/CDK6 signaling pathway.ConclusionsTherefore, our studies suggested that PSMC2 may act as a tumor promotor in the development and progression of prostate cancer, and could be considered as a novel therapeutic target for prostate cancer treatment.

Highlights

Prostate cancer is the most common malignant tumor of male genitourinary system, molecular mechanism of which is still not clear
Chen et al Cancer Cell Int (2021) 21:235 endocrine therapy, most prostate cancer patients will progress to castration-resistant prostate cancer, which is insensitive to chemotherapy and radiotherapy, suffering poor prognosis due to the lacking of effective therapy and the tendency of metastasis [9,10,11]
The silencing of PSMC2 led to the inhibition of proliferation and colony formation in prostate cancer cells we aimed to investigate the specific effects of PSMC2 in cancer of the prostate

Summary

Introduction

Prostate cancer is the most common malignant tumor of male genitourinary system, molecular mechanism of which is still not clear. PSMC2 (proteasome 26S subunit ATPase 2) is a key member of the 19S regulatory subunit of 26S proteasome, whose relationship with prostate cancer is rarely studied. Prostate cancer is the most common malignant tumor of male genitourinary system [1]. In United States, prostate cancer has been identified as the most common malignant tumor in men, accounting for 19% of morbidity of male cancer, which is the second most fatal cancer in. PSMC2 (proteasome 26S subunit ATPase 2), located in 7q22.1-q22.3 of the genome, is a key member of the 19S regulatory subunit of 26S proteasome, responsible for catalyzing the unfolding and translocation of substrates into the 20S proteasome [19]. Despite that PSMC2 is considered to be a newly discovered gene closely related to human cancer, its relationship with prostate cancer is still unclear

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