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Novel Protein Arginine Methyltransferase 8 Isoform Is Essential for Cell Proliferation
Author(s) -
Hernandez Sarah,
Dominko Tanja
Publication year - 2016
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25508
Subject(s) - biology , downregulation and upregulation , cell growth , microbiology and biotechnology , stem cell , gene knockdown , cell , phenotype , arginine , cell culture , genetics , gene , amino acid
ABSTRACT Identification of molecular mechanisms that regulate cellular replicative lifespan is needed to better understand the transition between a normal and a neoplastic cell phenotype. We have previously reported that low oxygen‐mediated activity of FGF2 leads to an increase in cellular lifespan and acquisition of regeneration competence in human dermal fibroblasts (iRC cells). Though cells display a more plastic developmental phenotype, they remain non‐tumorigenic when injected into SCID mice (Page et al. [2009] Cloning Stem Cells 11:417–426; Page et al. [2011] Eng Part A 17:2629–2640) allowing for investigation of mechanisms that regulate increased cellular lifespan in a non‐tumorigenic system. Analysis of chromatin modification enzymes by qRT‐PCR revealed a 13.3‐fold upregulation of the arginine methyltransferase PRMT8 in iRC cells. Increased protein expression was confirmed in both iRC and human embryonic stem cells—the first demonstration of endogenous human PRMT8 expression outside the brain. Furthermore, iRC cells express a novel PRMT8 mRNA variant. Using siRNA‐mediated knockdown we demonstrated that this novel variant was required for proliferation of human dermal fibroblasts (hDFs) and grade IV glioblastomas. PRMT8 upregulation in a non‐tumorigenic system may offer a potential diagnostic biomarker and a therapeutic target for cells in pre‐cancerous and cancerous states. J. Cell. Biochem. 117: 2056–2066, 2016. © 2016 Wiley Periodicals, Inc.