Potential role for microRNA-16 (miR-16) and microRNA-93 (miR-93) in diagnosis and prediction of disease progression in mycosis fungoides in Egyptian patients

PLoS One. 2019 Oct 24;14(10):e0224305. doi: 10.1371/journal.pone.0224305. eCollection 2019.

Abstract

Mycosis Fungoides (MF) is the most common type of cutaneous T-cell lymphomas. Early stage patients are treated with topical therapies and have normal life expectancy whereas patients with advanced disease encounter frequent relapses and have a five-year survival rate that does not exceed 15%. The aim of the present study was to characterize the expression of microRNA-16 (miR-16) and microRNA-93 (miR-93) in early and advanced cases of MF in relation to the clinicopathological parameters. Ten skin biopsies of early and advanced MF were investigated for the expression of miR-16 and miR-93 using RT-PCR. Immunohistochemical expression of apoptosis markers (BCL-2 and Survivin) were also investigated in the studied cases compared to normal skin and eczema biopsies. In the present study, BCL-2 and Survivin showed strong positive expression on neoplastic lymphocytes in all cases of MF regardless of their stage. We have also shown that miR-16 was significantly upregulated in advanced cases of MF compared to cases with early disease (p-value was less than 0.05). However, expression of miR-16 did not show any statistically significant correlation with age, gender, or expression of apoptotic markers. On the other hand, the expression of miR-93 showed significant downregulation in all lymphoma cases irrespective of their stage, compared to normal and eczema cases. Our results suggest that upregulation of miR-16 could be used to predict an aggressive course of the disease. We also suggest that miR-93 downregulation could serve as possible tool for establishing early diagnosis in early challenging cases. Our findings also provide consistent evidence that the anti-apoptotic molecules may play an important role in the pathogenesis of this type of cutaneous lymphomas and promote the idea that their inhibition could be an interesting novel therapeutic strategy in the treatment of MF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Disease Progression*
  • Egypt
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • Mycosis Fungoides / diagnosis*
  • Mycosis Fungoides / genetics*
  • Mycosis Fungoides / metabolism
  • Mycosis Fungoides / pathology
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Skin Neoplasms / diagnosis*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Survivin / metabolism

Substances

  • BCL2 protein, human
  • MIRN16 microRNA, human
  • MIRN93 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • Survivin

Grants and funding

This project was funded by the University of Sharjah research funding program, Project No 1701090215-P (http://www.sharjah.ac.ae/en/Research/rf/Pages/default.aspx). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.