Abstract

Proteasome α5 subunit (PSMA5) is related to poor prognosis in various cancers. The first therapeutic proteasome inhibitor, bortezomib, induces apoptosis, suppressing cell growth in many tumor types. However, the effects of PSMA5 and bortezomib in prostate cancer (PCa) are still unknown. In this study, we investigated whether PSMA5 is associated with the tumorigenic progression and the interaction of PSMA5 with bortezomib in PCa. We knocked down PSMA5 with siRNA and studied the changes in cell viability and motility with Cell Counting Kit-8, quantitative PCR, fluorescence-activated cell sorting, scratch, and invasion assays. We also investigated the effect of PSMA5 in PCa cells treated with bortezomib and in those that are resistant to bortezomib. We found that silencing PSMA5 inhibited cell proliferation, induced apoptosis, restricted cell migration and invasion, and demonstrated a coordinated effect with bortezomib. Cells resistant to bortezomib gained sensitivity to bortezomib after PSMA5 was knocked down. Our results show, for the first time, that PSMA5 promotes the tumorigenic process of PCa and is linked to bortezomib resistance.

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