MicroRNA expression profiling and DNA methylation signature for deregulated microRNA in cutaneous T-cell lymphoma

J Invest Dermatol. 2015 Apr;135(4):1128-1137. doi: 10.1038/jid.2014.487. Epub 2014 Nov 18.

Abstract

MicroRNAs usually regulate gene expression negatively, and aberrant expression has been involved in the development of several types of cancers. Microarray profiling of microRNA expression was performed to define a microRNA signature in a series of mycosis fungoides tumor stage (MFt, n=21) and CD30+ primary cutaneous anaplastic large cell lymphoma (CD30+ cALCL, n=11) samples in comparison with inflammatory dermatoses (ID, n=5). Supervised clustering confirmed a distinctive microRNA profile for cutaneous T-cell lymphoma (CTCL) with respect to ID. A 40 microRNA signature was found in MFt including upregulated onco-microRNAs (miR-146a, miR-142-3p/5p, miR-21, miR-181a/b, and miR-155) and downregulated tumor-suppressor microRNAs (miR-200ab/429 cluster, miR-10b, miR-193b, miR-141/200c, and miR-23b/27b). Regarding CD30+ cALCL, 39 differentially expressed microRNAs were identified. Particularly, overexpression of miR-155, miR-21, or miR-142-3p/5p and downregulation of the miR-141/200c clusters were observed. DNA methylation in microRNA gene promoters, as expression regulatory mechanism for deregulated microRNAs, was analyzed using Infinium 450K array and approximately one-third of the differentially expressed microRNAs showed significant DNA methylation differences. Two different microRNA methylation signatures for MFt and CD30+ cALCL were found. Correlation analysis showed an inverse relationship for microRNA promoter methylation and microRNA expression. These results reveal a subgroup-specific epigenetically regulated microRNA signatures for MFt and CD30+ cALCL patients.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cell Line, Tumor
  • Cluster Analysis
  • CpG Islands
  • DNA Methylation*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Ki-1 Antigen / metabolism
  • Lymphoma, T-Cell, Cutaneous / genetics*
  • Lymphoma, T-Cell, Cutaneous / metabolism
  • Lymphomatoid Papulosis / genetics
  • Lymphomatoid Papulosis / metabolism
  • Lymphoproliferative Disorders / genetics
  • Lymphoproliferative Disorders / metabolism
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Mycosis Fungoides / genetics
  • Mycosis Fungoides / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic
  • Retrospective Studies
  • Young Adult

Substances

  • Ki-1 Antigen
  • MicroRNAs