Mycosis fungoides progression could be regulated by microRNAs

PLoS One. 2018 Jun 12;13(6):e0198477. doi: 10.1371/journal.pone.0198477. eCollection 2018.

Abstract

Differentiating early mycosis fungoides (MF) from inflammatory dermatitis is a challenge. We compare the differential expression profile of early-stage MF samples and benign inflammatory dermatoses using microRNA (miRNA) arrays. 114 miRNAs were found to be dysregulated between these entities. The seven most differentially expressed miRNAs between these two conditions were further analyzed using RT-PCR in two series comprising 38 samples of early MFs and 18 samples of inflammatory dermatitis. A series of 51 paraffin-embedded samples belonging to paired stages of 16 MF patients was also analyzed. MiRNAs 26a, 222, 181a and 146a were differentially expressed between tumoral and inflammatory conditions. Two of these miRNAs (miRNA-181a and miRNA-146a) were significantly deregulated between early and advanced MF stages. Bioinformatic analysis showed FOXP3 expression to be regulated by these miRNAs. Immunohistochemistry revealed the level of FOXP3 expression to be lower in tumoral MFs than in plaque lesions in paraffin-embedded tissue. A functional study confirmed that both miRNAs diminished FOXP3 expression when overexpressed in CTCL cells. The data presented here suggest that the analysis of a restricted number of miRNAs (26a, 222, 181a and 146a) could be sufficient to differentiate tumoral from reactive conditions. Moreover, these miRNAs seem to be involved in MF progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Mycosis Fungoides / genetics*
  • Mycosis Fungoides / metabolism
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism

Substances

  • 3' Untranslated Regions
  • Biomarkers, Tumor
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • MicroRNAs

Grants and funding

This work was supported by grants from the Instituto de Salud Carlos III, from the Ministerio de Economía, Industria y Competitividad (SAF2013-47416-R, CIBERONC-ISCIII, ISCIII-MINECO AES-FEDER (Plan Estatal I+D+I 2013-2016): PI14/00221, PIE14/0064, PIE15/0081 and PIE16/01294) and the Asociación Española Contra el Cancer, Spain. The Instituto de Investigación Marqués de Valdecilla (IDIVAL) is partly funded by the Sociedad para el Desarrollo Regional de Cantabria (SODERCAN).