SwePub
Sök i LIBRIS databas

  Utökad sökning

onr:"swepub:oai:gup.ub.gu.se/201103"
 

Sökning: onr:"swepub:oai:gup.ub.gu.se/201103" > PRMT2 and ROR gamma...

PRMT2 and ROR gamma Expression Are Associated With Breast Cancer Survival Outcomes

Oh, T. G. (författare)
Bailey, P. (författare)
Dray, E. (författare)
visa fler...
Smith, A. G. (författare)
Goode, J. (författare)
Eriksson, N. (författare)
Funder, J. W. (författare)
Fuller, P. J. (författare)
Simpson, E. R. (författare)
Tilley, W. D. (författare)
Leedman, P. J. (författare)
Clarke, C. L. (författare)
Grimmond, S. (författare)
Dowhan, D. H. (författare)
Muscat, George (författare)
Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
visa färre...
 (creator_code:org_t)
 
visa fler...
 
visa färre...
2014
2014
Engelska.
Ingår i: Molecular Endocrinology. - 0888-8809. ; 28:7, s. 1166-1185
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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 retinoid-related orphan receptor-gamma (ROR gamma) is inversely correlated in estrogen receptor-positive breast cancer and increased ROR gamma 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, ROR gamma, the cell-cycle regulation, DNA repair circuits, and breast cancer survival outcomes.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

ORPHAN NUCLEAR RECEPTOR
GENE-EXPRESSION
R/BIOCONDUCTOR PACKAGE
ARGININE METHYLATION
HOMOLOGOUS RECOMBINATION
MOLECULAR-BASIS
IDENTIFICATION
REGULATOR
MODELS
CELLS
Endocrinology & Metabolism

Publikations- och innehållstyp

ref (ämneskategori)
art (ämneskategori)

Hitta via bibliotek

Till lärosätets databas

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy