PHF19 activates hedgehog signaling and promotes tumorigenesis in hepatocellular carcinoma.
Aberrant activation of Hedgehog-Gli1 signaling and accumulation of Gli1 in hepatocellular carcinoma (HCC) are frequently observed. However, the mechanisms leading to the overactivation of this signaling pathway are not fully understood. In this study, we show that the short isoform of PHD finger protein 19 (PHF19) interacts with ?-TrCP, the ... E3 ligase of Gli1, and that knocking down PHF19 promotes the ubiquitination of Gli1. In a biological function study, PHF19 was found to promote the growth of HCC cells both in liquid culture and in soft agar. Moreover, knocking out PHF19 in a HCC mouse model (MycF/F) using the hydrodynamic method inhibited tumorigenesis and improved survival. Taken together, these results demonstrate that PHF19 promotes the growth of HCC cells by activating the Hedgehog signaling pathway.
Mesh Terms:
Animals, Carcinoma, Hepatocellular, Cell Line, Tumor, Cell Movement, Cell Proliferation, DNA-Binding Proteins, Forkhead Box Protein M1, Gene Expression Regulation, Neoplastic, Hedgehog Proteins, Hepatocytes, Humans, Liver Neoplasms, Mice, Patched-1 Receptor, Protein Processing, Post-Translational, RNA, Small Interfering, Signal Transduction, Survival Analysis, Transcription Factors, Tumor Burden, Ubiquitination, Xenograft Model Antitumor Assays, Zinc Finger Protein GLI1
Animals, Carcinoma, Hepatocellular, Cell Line, Tumor, Cell Movement, Cell Proliferation, DNA-Binding Proteins, Forkhead Box Protein M1, Gene Expression Regulation, Neoplastic, Hedgehog Proteins, Hepatocytes, Humans, Liver Neoplasms, Mice, Patched-1 Receptor, Protein Processing, Post-Translational, RNA, Small Interfering, Signal Transduction, Survival Analysis, Transcription Factors, Tumor Burden, Ubiquitination, Xenograft Model Antitumor Assays, Zinc Finger Protein GLI1
Exp Cell Res
Date: Dec. 01, 2020
PubMed ID: 34129846
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