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Survivin controls biogenesis of microRNA in smokers: A link to pathogenesis of rheumatoid arthritis.

Journal article
Authors Karin Andersson
Minna Turkkila
Malin Erlandsson
Apostolos Bossios
Sofia Silfverswärd Lindblad
Dan Hu
Linda Ekerljung
Carina Malmhäll
Howard L. Weiner
Bo Lundbäck
Maria Bokarewa
Published in Biochimica et biophysica acta
Volume 1863
Issue 3
Pages 663–673
ISSN 0006-3002
Publication year 2017
Published at Krefting Research Centre
Institute of Medicine, Department of Rheumatology and Inflammation Research
Pages 663–673
Language en
Links dx.doi.org/10.1016/j.bbadis.2016.11...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Rheumatology and Autoimmunity

Abstract

MicroRNAs (miRs) represent a part of epigenetic control of autoimmunity gaining increasing attention in rheumatoid arthritis (RA). Since cigarette smoking plays important role in RA pathogenesis and reprograms transcriptional profile of miRNAs, we ask if the onco-protein survivin, a novel biomarker of RA, may provide a link between smoking and miRNA. Studying survivin expression in leukocytes of 144 female RA patients we observed that smoking patients had higher survivin transcription and a remarkable spreading of survivin isoforms. This was associated with restricted pattern and low production of miRs. Additionally, miRNA processing enzymes Dicer and DGRC8 were decreased in the patients with survivin isoform spreading. The direct contribution of survivin in miRs biogenesis was confirmed by a massive increase of miRs production following inhibition of survivin in leukocyte cultures. Dicer is shown to mediate these effects of survivin. Chromatin immunoprecipitation analysis demonstrated binding of survivin to the Dicer promoter region. Dicer expression increased 5-folds following survivin inhibition. Taken together, this study presents experimental evidence of a novel cellular function of survivin, control of miRs biogenesis. Up-regulation of survivin in smokers suggests its role as effector of the adverse epigenetic control in RA.

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