ZNF191 Inhibits Hepatocellular Carcinoma Metastasis via DLG1-mediated YAP1 Inactivation

Abstract

Searching targets for hepatocellular carcinoma (HCC) treatment, we identified zinc finger protein 191 (ZNF191) as a suppressor against HCC metastasis. Over-expressing ZNF191 in HCC cells impaired cell motility, while ZNF191 depletion promoted HCC cell migration in vitro and metastasis in vivo through triggering yes-associated protein 1 (YAP1) signaling. Chromatin immunoprecipitation-sequencing (ChIP-seq) revealed that ZNF191 specifically bound to the promoter of Discs, Large homolog 1 (DLG1), a cell polarity maintainer and a negative regulator of YAP1. Double-knockdown experiments showed that DLG1 was not only the mediator of ZNF191s function to suppress migration but also a link between ZNF191 and YAP1 signaling. ZNF191 was down-regulated in metastatic HCCs, correlating positively with DLG1 levels and inversely with YAP1 activation. Our findings indicate ZNF191 functions as a metastasis suppressor via DLG1-mediated YAP1 signaling inactivation.