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

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 Pduanyu3712 through protein affinity purification. Although Pduanyu3712 did not mono-ADP-ribosylate FHL2 in vitro and in vivo, Pduanyu3712 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 Pduanyu3712 enzymatic activity. We also provided evidence that Pduanyu3712 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 Pduanyu3712 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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