PRMT2 and RORλ expression are associated with breast cancer survival outcomes

Oh, Tae Gyu, Bailey, Peter, Dray, Eloise, Smith, Aaron G., Goode, Joel, Eriksson, Natalie, Funder, John W., Fuller, Peter J., Simpson, Evan R., Tilley, Wayne D., Leedman, Peter J., Clarke, Christine L., Grimmond, Sean, Dowhan, Dennis H. and Muscat, George E. O. (2014) PRMT2 and RORλ expression are associated with breast cancer survival outcomes. Molecular Endocrinology, 28 7: 1166-1185. doi:10.1210/me.2013-1403


Author Oh, Tae Gyu
Bailey, Peter
Dray, Eloise
Smith, Aaron G.
Goode, Joel
Eriksson, Natalie
Funder, John W.
Fuller, Peter J.
Simpson, Evan R.
Tilley, Wayne D.
Leedman, Peter J.
Clarke, Christine L.
Grimmond, Sean
Dowhan, Dennis H.
Muscat, George E. O.
Title PRMT2 and RORλ expression are associated with breast cancer survival outcomes
Journal name Molecular Endocrinology   Check publisher's open access policy
ISSN 1944-9917
0888-8809
Publication date 2014
Sub-type Article (original research)
DOI 10.1210/me.2013-1403
Open Access Status
Volume 28
Issue 7
Start page 1166
End page 1185
Total pages 20
Place of publication Chevy Chase, MD, United States
Publisher Endocrine Society
Collection year 2015
Language eng
Abstract Protein arginine methyltransferases (PRMTs) methylate arginine residues on histones and target transcription factors that play critical roles in many cellular processes, including gene transcription, mRNA splicing, proliferation, and differentiation. Recent studies have linked PRMT-dependent epigenetic marks and modifications to carcinogenesis and metastasis in cancer. However, the role of PRMT2-dependent signaling in breast cancer remains obscure. We demonstrate PRMT2 mRNA expression was significantly decreased in breast cancer relative to normal breast. Gene expression profiling, Ingenuity and protein-protein interaction network analysis after PRMT2-short interfering RNA transfection into MCF-7 cells, revealed that PRMT2- dependent gene expression is involved in cell-cycle regulation and checkpoint control, chromosomal instability, DNA repair, and carcinogenesis. For example, PRMT2 depletion achieved the following: 1) increased p21 and decreased cyclinD1 expression in (several) breast cancer cell lines, 2) decreased cell migration, 3) induced an increase in nucleotide excision repair and homologous recombination DNA repair, and 4) increased the probability of distance metastasis free survival (DMFS). The expression of PRMT2 and retinoidrelated orphan receptor-λ (RORλ) is inversely correlated in estrogen receptor-positive breast cancer and increased RORλ expression increases DMFS. Furthermore, we found decreased expression of the PRMT2- dependent signature is significantly associated with increased probability of DMFS. Finally, weighted gene coexpression network analysis demonstrated a significant correlation between PRMT2-dependent genes and cell-cycle checkpoint, kinetochore, and DNA repair circuits. Strikingly, these PRMT2-dependent circuits are correlated with pan-cancer metagene signatures associated with epithelial-mesenchymal transition and chromosomal instability. This study demonstrates the role and significant correlation between a histone methyltransferase (PRMT2)-dependent signature, RORλ, the cell-cycle regulation, DNA repair circuits, and breast cancer survival outcomes.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Biomedical Sciences Publications
Institute for Molecular Bioscience - Publications
 
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