Downregulation of miR-542-3p Contributes to Apoptosis Resistance in Dermal Fibroblasts from Systemic Sclerosis Patients via Survivin Overexpression

  • Pegah Vahidi Manesh Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Department of Cell and Molecular Biology, University of Tehran, Tehran, Iran
  • Ali Farazmand Department of Cell and Molecular Biology, University of Tehran, Tehran, Iran
  • Farhad Gharibdoost Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
  • Negar Vanaki Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
  • Shayan Mostafaei Department of Community Medicine, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
  • Hoda Kavosi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
  • Mohammad Bagher Mahmoudi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
  • Mahdi Mahmoudi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Keywords: Apoptosis, miR-542-3p, Survivin, Systemic sclerosis

Abstract

Systemic sclerosis (SSc) is characterized by excessive production of collagens by fibroblasts that leads to vast fibrosis. Resistance to apoptosis is one of the possible underlying mechanisms of fibrosis in these patients. Survivinis involved in inhibition of apoptosis and aberrantly functions in SSc. Since dysregulation of survivin-targeting microRNAs (miRNAs) has frequently been observed in cancer and some autoimmune disorders, this study aimed to investigate their expression status in dermal fibroblasts from SSc patients. DiffuseSSc patients were selected according to American College of Rheumatology criteria. Isolated fibroblasts from 10 SSc and 10 healthy skin biopsies were cultured. After examining purity of the cells, mRNA and miRNAs extraction was performed followed by complementary DNA (cDNA) synthesis. Relative expressions ofsurvivin mRNA, miR-16-5p, miR-320a, miR-218-5p, miR-708-5p and miR-542-3p were analyzed using real time PCR. Survivin mRNA expression was significantly 1.85-fold upregulated in fibroblasts from SSc patients compared with healthy controls (p=0.046). Among the studied miRNAs, miR-542-3p expression was significantly decreased (p=0.033), while enhanced expression of miR-708-5p was observed in SSc fibroblasts (p=0.05) in comparison to healthy subjects. Downregulation of miR-542-3p significantly correlated with survivin overexpression (r=˗0.45, p=0.049). Downregulation of miR-542-3p that is correlated with higher surviving expression levels might be a possible cause of apoptosis resistance in SSc fibroblasts, hence providing a new understanding of the disease pathogenesis.

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Published
2019-04-01
How to Cite
1.
Vahidi Manesh P, Farazmand A, Gharibdoost F, Vanaki N, Mostafaei S, Kavosi H, Mahmoudi MB, Mahmoudi M. Downregulation of miR-542-3p Contributes to Apoptosis Resistance in Dermal Fibroblasts from Systemic Sclerosis Patients via Survivin Overexpression. Iran J Allergy Asthma Immunol. 18(2):173-181.
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Original Article(s)