Inhibition of ubiquitin ‑specific protease 14 promotes connexin 32 internalization and counteracts cisplatin cytotoxicity in human ovarian cancer cells.

Inhibition of ubiquitin‑specific protease 14 promotes connexin 32 internalization and counteracts cisplatin cytotoxicity in human ovarian cancer cells. Oncol Rep. 2019 Jul 15;: Authors: Luo H, Wang X, Ge H, Zheng N, Peng F, Fu Y, Tao L, Wang Q Abstract Although cisplatin is one of the most accepted therapies for ovarian cancer, recurrence and drug resistance remain problematic. Both the ubiquitin‑proteasome system (UPS) and connexin (Cx) are closely related to tumor progression. However, the role of ubiquitin‑specific protease 14 (USP14) and Cx in mediating drug resistance remains unclear. In the present study, we aimed to determine whether USP14 is involved in cisplatin resistance and modulates the internalization of connexin 32 (Cx32) in ovarian cancer. The results of the deubiquitinase (DUB) trap assay and western blot analysis revealed that the expression and activity levels of USP14 were downregulated in A2780 cisplatin‑resistant cells (A2780‑CDDP) relative to these levels in A2780 cisplatin‑sensitive cells (A2780). CCK‑8 assay results showed that inhibition of USP14 by a specific inhibitor or siRNA decreased cisplatin cytotoxicity in A2780 cells. Additionally, USP14 inhibition increased the expression of Cx32 without changing its mRNA and ubiquitination levels, as showed by Real‑time qPCR and immunoprecipitation assay respectively. Cisplatin resistance induced by USP14 inhibition was counteracted by Cx32 kn...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research