PRMT6 overexpression upregulates TSP-1 and downregulates MMPs: its implication in motility and invasion.

Abstract

In this study, we investigate the molecular mechanism by which protein arginine methyltransferase 6 (PRMT6) exerts anti-invasiveness effect against breast cancer cells and prostate cancer cells. PRMT6 has been known to be responsible for asymmetric dimethylation of histone H3 at R2 (H3R2me2a). To investigate the biological role of PRMT6, we first established stable cell lines expressing GFP-PRMT6 with MCF7 and PC3 cells. Growth rates and colony forming abilities of PRMT6-overexpressing cells were significantly retarded compared to control GFP expressing cells. This growth retardation seems to be associated with p21(WAF1) induction. In addition, our data show that migration and invasion of prostate cancer cells was strongly suppressed by PRMT6 overexpression. In parallel, the levels of thrombospondin-1 (TSP-1), a potent natural inhibitor of angiogenesis, were highly up-regulated in both PRMT6-overexpressing cells. Furthermore, this suppression of migration and invasion by PRMT6 overexpression was significantly rescued by specific knock-down of TSP-1. Concomitantly, down-regulations of MMP-2 and -9 were observed in PRMT6-overexpressing cells. Taken together, our data demonstrate that PRMT6 overexpression is associated with regulation of motility and invasion through up-regulation of TSP-1 and down-regulation of MMPs in human cancer cells.

• Authors: Nam Hyun Kim, Su-Nam Kim, Dong-Wan Seo, Jeung-Whan Han, Yong Kee Kim
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 432 Issue 1 Pg. 60-5 (Mar 01 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 23380452 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Nuclear Proteins
• Thrombospondin 1
• PRMT6 protein, human
• Protein-Arginine N-Methyltransferases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Breast Neoplasms (metabolism, pathology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Down-Regulation
• Female
• Gene Knockdown Techniques
• Humans
• MCF-7 Cells
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Neoplasm Invasiveness
• Nuclear Proteins (biosynthesis, genetics)
• Prostatic Neoplasms (metabolism, pathology)
• Protein-Arginine N-Methyltransferases (biosynthesis, genetics)
• Thrombospondin 1 (biosynthesis, genetics)