Reversal of sorafenib resistance in hepatocellular carcinoma: epigenetically regulated disruption of 14-3-3η/hypoxia-inducible factor-1α.

ABSTRACT: Sorafenib resistance is one of the main obstacles to the treatment of advanced/recurrent hepatocellular carcinoma (HCC). Here, sorafenib-resistant HCC cells and xenografts in nude mice were used as experimental models. A cohort of patients with advanced recurrent HCC who were receiving sorafenib therapy was used to assess the clinical significance of this therapy. Our data showed that 14-3-3η maintained sorafenib resistance in HCC. An analysis of the underlying molecular mechanisms revealed that 14-3-3η stabilizes hypoxia-inducible factor 1α (HIF-1α) through the inhibition of ubiquitin-dependent proteasome protein degradation, which leads to the maintenance of cancer stem cell (CSC) properties. We further found that microRNA-16 (miR-16) is a competent miRNA that reverses sorafenib resistan

SUBMITTER: Qiu Y 

PROVIDER: S-EPMC6642098 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature