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

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

Author information

1
Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Spain. Electronic address: jsandoval@idibell.cat.
2
Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Spain.
3
Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain.
4
Servei de Dermatologia i Patologia, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
5
Servicio de Dermatologia, Hospital 12 de Octubre, University Complutense Madrid, Madrid, Spain.
6
Servicio de Dermatologia, Hospital General de Valencia, Valencia, Spain.
7
Servei de Dermatologia, Hospital de Sant Pau, Barcelona, Spain.
8
Servei de Dermatologia, Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
9
Servei d'Anàlisi de Microarrays, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
10
Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Spain; Department of Physiological Science II, School of Medicine, University of Barcelona, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
11
Servei de Dermatologia, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain.
12
Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain; Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
13
Servei de Dermatologia, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain; Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Electronic address: fgallardo@parcdesalutmar.cat.

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.

PMID:
25405321
DOI:
10.1038/jid.2014.487
[Indexed for MEDLINE]
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