DUB3/KLF4 combats tumor growth and chemoresistance in hepatocellular carcinoma.

ABSTRACT: This study aimed to investigate the role of deubiquitinating enzyme 3 (DUB3) in the regulation of Krüppel-like factor 4 (KLF4) expression in hepatocellular carcinoma (HCC). Gain- and loss-of-function assay, luciferase reporter assay, co-immunoprecipitation, and intracellular and extracellular deubiquitination assays were conducted in vitro. A tumor xenograft mouse model was established. The expression of DUB3 and KLF4 was examined in HCC patient specimens. The results showed that DUB3 upregulated KLF4 expression by deubiquitinating and stabilizing KLF4 protein in HCC cells through binding with KLF4. DUB3 inhibited HCC cell proliferation in vitro and tumor growth in vivo while enhancing the chemosensitivity of HCC cells in a KLF4-dependent manner. Furthermore, KLF4 promoted DUB3 transcripti

SUBMITTER: Jia X 

PROVIDER: S-EPMC8983766 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature