title: Novel Protein Arginine Methyltransferase 8 Isoform Is Essential for Cell Proliferation.
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.
authors: Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, MA.
authors: Sarah
authors: S
authors: Hernandez
authors: Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, MA.|Bioengineering Institute, Worcester Polytechnic Institute, Worcester, MA.|Center for Biomedical Sciences and Engineering, University of Nova Gorica, Vipava, Slovenia.
authors: Tanja
authors: T
authors: Dominko
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology*; D020405:Dermis / Q000201:enzymology*; D005347:Fibroblasts / Q000201:enzymology* / Q000637:transplantation; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D064593:Heterografts; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D011484:Protein-Arginine N-Methyltransferases / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; C505447:PRMT8 protein, human; D011484:Protein-Arginine N-Methyltransferases
keywords: CANCER BIOLOGY; PROLIFERATION; PROTEIN METHYLATION; REPROGRAMMING; SENESCENCE