PRMT2 accelerates tumorigenesis of hepatocellular carcinoma by activating Bcl2 via histone H3R8 methylation.

Abstract

Protein arginine methyltransferases (PRMTs) have been implicated in the development of various cancers. PRMT2, a member of the type I PRMT family, is overexpressed in multiple tumors. However, the expression and role of PRMT2 in hepatocellular carcinoma (HCC) have not been studied. Here, we discovered that PRMT2 expression is elevated in HCC tissues compared to the corresponding non-tumor tissues, and PRMT2 overexpression is an independent predictor of poor prognosis in HCC patients. Depletion of PRMT2 in HCC cell lines inhibited their cell growth and induced apoptosis. Mechanistic investigations showed that PRMT2 is responsible for H3R8 asymmetric methylation (H3R8me2a). H3R8me2a enrichment at the Bcl2 promoter increases its accessibility to STAT3, promoting Bcl2 gene expression. In addition, our results confirmed that the catalytically inactive mutant of PRMT2 or the type I PRMT inhibitor MS023 impaired the pro-tumorigenic functions of PRMT2 in HCC cells. Overall, our findings showed that PRMT2 functions as an oncogenic gene in HCC, revealing its potential as a novel therapeutic target in HCC.

• Authors: Guohui Hu, Chen Yan, Peiyi Xie, Yan Cao, Jia Shao, Jin Ge
• Journal: Experimental cell research (Exp Cell Res) Vol. 394 Issue 2 Pg. 112152 (09 15 2020) ISSN: 1090-2422 [Electronic] United States
• PMID: 32574605 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Histones
• Intracellular Signaling Peptides and Proteins
• Proto-Oncogene Proteins c-bcl-2
• Arginine
• PRMT2 protein, human
• Protein-Arginine N-Methyltransferases

Topics

• Animals
• Apoptosis (genetics)
• Arginine (metabolism)
• Carcinogenesis (metabolism, pathology)
• Carcinoma, Hepatocellular (enzymology, genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Histones (metabolism)
• Humans
• Intracellular Signaling Peptides and Proteins (genetics, metabolism)
• Liver Neoplasms (enzymology, genetics, pathology)
• Male
• Methylation
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Promoter Regions, Genetic
• Protein-Arginine N-Methyltransferases (genetics, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Up-Regulation (genetics)