TAZ-induced Cybb contributes to liver tumor formation in non-alcoholic steatohepatitis.

ABSTRACT:

Background & aims

Non-alcoholic steatohepatitis (NASH) is a leading cause of hepatocellular carcinoma (HCC), but mechanisms linking NASH to eventual tumor formation remain poorly understood. Herein, we investigate the role of TAZ/WWTR1, which is induced in hepatocytes in NASH, in the progression of NASH to HCC.

Methods

The roles of hepatocyte TAZ and its downstream targets were investigated in diet-induced and genetic models of NASH-HCC using gene-targeting, adeno-associated virus 8 (AAV8)-H1-mediated gene silencing, or AAV8-TBG-mediated gene expression. The biochemical signature of the newly elucidated pathway was probed in liver specimens from humans with NASH-HCC.

Results

When hepatocyte-TAZ was silenced in mice with pre-tumor NASH using AAV8-H1-shTaz (short-hairpi

SUBMITTER: Wang X 

PROVIDER: S-EPMC8934258 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature