Proteasome inhibitor-resistant cells cause EMT-induction via suppression of E-cadherin by miR-200 and ZEB1.

Proteasome inhibitor-resistant cells cause EMT-induction via suppression of E-cadherin by miR-200 and ZEB1. Int J Oncol. 2015 Mar 4; Authors: Asakura T, Yamaguchi N, Ohkawa K, Yoshida K Abstract Downregulation of E-cadherin (gene: CDH1) plays an important role in epithelial-mesenchymal transition (EMT), which is critical for normal development and disease states. As a result of long-term treatment of endometrial carcinoma Ishikawa cells with epoxomicin (EXM), the cells exhibited the phenotype for EXM-resistance (Ish/EXM cells). Moreover, CDH1 mRNA and its protein were suppressed and EMT was induced in Ish/EXM cells. Ish/EXM cells exhibited drug-resistance to other proteasome inhibitors, MG-132, PSI and PS-341 (Bortezomib). The proteasome inhibitor-resistant cells acquired invasiveness as a result of the chemotherapy. In Ish/EXM cells, E-cadherin was suppressed by upregulation of its transcriptional repressor ZEB1. Furthermore, expression of the miR-200 family (miR-200a, miR-200b, miR-200c and miR-141) found in Ishikawa cells was suppressed in Ish/EXM cells. Overexpression of the miR-200 family in Ish/EXM cells caused by transfection with the pre-miR-200 family induced downregulation of ZEB1 and enhanced expression of E-cadherin. Conversely, suppression of miR-200 expression in the Ishikawa cells by transfection with anti-miR-200 elevated the expression of ZEB1 and suppressed the expression of E-cadherin. These results suggest that ac...
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research