Targeting endothelin 1 receptor-miR-200b/c-ZEB1 circuitry blunts metastatic progression in ovarian cancer.

ABSTRACT: Identification of regulatory mechanisms underlying the poor prognosis of ovarian cancer is necessary for diagnostic and therapeutic implications. Here we show that endothelin A receptor (ET_AR) and ZEB1 expression is upregulated in mesenchymal ovarian cancer and correlates with poor prognosis. Notably, the expression of ET_AR and ZEB1 negatively correlates with miR-200b/c. These miRNAs, besides targeting ZEB1, impair ET_AR expression through the 3'UTR binding. ZEB1, in turn, restores ET_AR levels by transcriptionally repressing miR-200b/c. Activation of ET_AR drives the expression of ZEB1 integrating the miR-200/ZEB1 double negative feedback loop. The ET_AR-miR-200b/c-ZEB1 circuit promotes epithelial-mesenchymal transition, cell p

SUBMITTER: Sestito R 

PROVIDER: S-EPMC7666224 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature