PARP12 (ARTD12) suppresses hepatocellular carcinoma metastasis through interacting with FHL2 and regulating its stability.

Cell Death & Disease
Changjuan ShaoJiaxue Wu

Abstract

PARP12 is a mono-ADP-ribosyltransferase, but its function remains largely unknown. Here, we identified four-and-a-half LIM-only protein 2 (FHL2) as a functional partner of PARP12 through protein affinity purification. Although PARP12 did not mono-ADP-ribosylate FHL2 in vitro and in vivo, PARP12 deficiency decreased the protein level of FHL2 by promoting its ubiquitination and increased the expression level of transforming growth factor beta1 (TGF-β1), which is independent of PARP12 enzymatic activity. We also provided evidence that PARP12 deficiency increased the migration and invasion of hepatocellular carcinoma (HCC) cells and promoted HCC metastasis in vivo by regulating the epithelial-mesenchymal transition process. These results indicated that PARP12 is a tumor suppressor that plays an important role in HCC metastasis through the regulation of FHL2 stability and TGF-β1 expression.

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Citations

Oct 17, 2019·Cells·Shuo TuXiaohua Yan
Mar 18, 2020·Reproduction in Domestic Animals = Zuchthygiene·Limeng ZhangShujun Tian
Feb 3, 2019·Biochemical Society Transactions·Giovanna Grimaldi, Daniela Corda
Jul 11, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Alex Boye

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Methods Mentioned

BETA
tandem affinity purification
affinity
immunoprecipitation
Co-IP
affinity purification
pull-down
pull down
ubiquitination
ELISA
PCR

Software Mentioned

GraphPad
GraphPad Prism
ImageJ

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