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

Karin M E Andersson, Minna Turkkila, Malin C Erlandsson, Apostolos Bossios, Sofia Töyrä Silfverswärd, Dan Hu, Linda Ekerljung, Carina Malmhäll, Howard L Weiner, Bo Lundbäck, Maria I Bokarewa

Journal: Biochimica et biophysica acta. Molecular basis of disease 2018;1863(3):663-673

PMID: 27915033

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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.

Address: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 480, 405 30 Gothenburg, Sweden. Electronic address: [email protected].; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 480, 405 30 Gothenburg, Sweden. Electronic address: [email protected].; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 480, 405 30 Gothenburg, Sweden. Electronic address: [email protected].; The Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 424, 405 30 Gothenburg, Sweden. Electronic address: [email protected].; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 480, 405 30 Gothenburg, Sweden. Electronic address: [email protected].; Center for Neurologic Diseases, Brigham&Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, US. Electronic address: [email protected].; The Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 424, 405 30 Gothenburg, Sweden. Electronic address: [email protected].; The Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 424, 405 30 Gothenburg, Sweden. Electronic address: [email protected].; Center for Neurologic Diseases, Brigham&Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, US. Electronic address: [email protected].; The Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 424, 405 30 Gothenburg, Sweden. Electronic address: [email protected].; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 480, 405 30 Gothenburg, Sweden. Electronic address: [email protected].

DOI: 10.1016/j.bbadis.2016.11.033

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https://scite.ai/reports/27915033

MeSH Terms: Adult, Aged, Arthritis, Rheumatoid, Cigarette Smoking, Female, Humans, Inhibitor of Apoptosis Proteins, MicroRNAs, Middle Aged, Protein Isoforms, Smokers, Survivin, Transcriptional Activation, Transcriptome