HIF-1/2α-Activated RNF146 Enhances the Proliferation and Glycolysis of Hepatocellular Carcinoma Cells via the PTEN/AKT/mTOR Pathway.

ABSTRACT: Hypoxia microenvironment, a critical feature of hepatocellular carcinoma, contributes to hepatocarcinogenesis, tumor progression and therapeutic resistance. Hypoxia-inducible factors (HIFs)-activated target genes are the main effectors in hypoxia-induced HCC progression. In this study, we identified ubiquitin E3 ligase ring finger protein 146 (RNF146) as a novel HIFs target gene. Either HIF-1α or HIF-2α knockdown significantly repressed hypoxia-induced RNF146 upregulation in Hep3B and Huh7 cells. TCGA data and our immunohistochemistry analysis consistently revealed the overexpression of RNF146 in HCC tissues. The upregulated expression of RNF146 was also detected in HCC cell lines. The high RNF146 level was correlated with poor clinical features and predicted a shorter overall survival of

SUBMITTER: Shen G 

PROVIDER: S-EPMC9200061 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature