MicroRNA expression profiling and DNA methylation signature for deregulated MicroRNA in cutaneous T-Cell Lymphoma

Sandoval, Juan ; Díaz-Lagares, Angel ; Salgado, Rocío ; Servitje, Octavio ; Climent, Fina ; Ortiz-Romero, Pablo L. ; Pérez-Ferriols, Amparo ; Garcia-Muret, Maria P. ; Estrach, Teresa ; Garcia, Mar ; Nonell, Lara ; Esteller, Manel ; Pujol, Ramon M. ; Espinet, Blanca ; Gallardo, Fernando

Resumen: 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.

Idioma: Inglés

DOI: 10.1038/jid.2014.487

Año: 2015

Publicado en: JOURNAL OF INVESTIGATIVE DERMATOLOGY 135, 4 (2015), 1128-1137
ISSN: 0022-202X

Factor impacto JCR: 6.915 (2015)

Categ. JCR: DERMATOLOGY rank: 1 / 61 = 0.016 (2015) - Q1 - T1

Factor impacto SCIMAGO: 2.66 - Biochemistry (Q1) - Molecular Biology (Q1) - Dermatology (Q1) - Cell Biology (Q1)

Tipo y forma: Article (Published version)