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

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1863

Article

Andersson, Karin M. E.¹  Turkkila, Minna¹  Erlandsson, Malin C.¹  Bossios, Apostolos^2,4  Silfversward, Sofia Toyra¹  Hu, Dan³  Ekerljung, Linda²  Malmhall, Carina²  Weiner, Howard L.³  Lundback, Bo²  Bokarewa, Maria I.¹ 

[1] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, POB 480, S-40530 Gothenburg, Sweden

[2] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Krefting Res Ctr,Dept Internal Med & Clin Nutr, POB 424, S-40530 Gothenburg, Sweden

[3] Harvard Med Sch, Brigham & Womens Hosp, Ctr Neurol Dis, 75 Francis St, Boston, MA 02115 USA

[4] Karolinska Inst, Dept Med, Unit Heart & Lung Dis, Stockholm, Sweden

关键词: Survivin;    Smoking;    miRNA;    Dicer;    Rheumatoid arthritis;   

DOI  :  10.1016/j.bbadis.2016.11.033

来源: Elsevier

【 摘 要 】

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. (C) 2016 The Authors. Published by Elsevier B.V.

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