miRNA expression profiling of mycosis fungoides

Abstract

MicroRNAs (miRNAs) are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many malignancies including lymphoma. However, the role of miRNAs in the pathogenesis of T-cell lymphoid malignancies is poorly understood. Previously we examined the miRNA profile of Sézary syndrome (Sz), a leukemia of skin-homing memory T cells. In this study we determined the complete miRNome of mycosis fungoides (MF), the most common type of cutaneous T cell lymphoma. The miRNA profile of skin biopsies from 19 patients with tumor stage MF and 12 patients with benign inflammatory dermatoses (eczema and lichen planus) were compared by microarray analysis. We identified 49 miRNAs that are differentially expressed in tumor stage MF compared to benign inflammatory dermatoses using ANOVA analysis (P < 0.05, Benjamini-Hochberg corrected). The majority of the differentially expressed miRNAs (30/49) were up-regulated in tumor stage MF. The most significant differentially expressed were miR-155 and miR-92a (both up-regulated in tumor stage MF), while miR-93 showed the highest up-regulation in tumor stage MF with a fold difference of 5.8. Differential expression of a selection of these miRNAs was validated by miRNA-Q-PCR on additional test groups (tumors and controls). None of the miRNAs up-regulated in tumor stage MF was previously shown to be up-regulated in Sz, and only 2 of the 19 miRNAs down-regulated in tumor stage MF were also down-regulated in Sz. Taken together this report is the first describing the miRNA signature of tumor stage MF.

Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Figures

Figure 1

Unsupervised cluster analysis tumor stage MF and benign inflammatory dermatoses. Heatmap representing miRNA array expression data of MF tumor samples (n = 19 depicted in blue) and benign inflammatory dermatosis samples (n = 12, depicted in yellow).

Figure 2

Expression levels of selected miRNAs as measured by miRNA‐Q‐PCR in an additional test group. Expression levels of miR‐93, miR‐155, miR‐92a, miR‐30b, miR‐16, miR‐30c and miR‐383 in tumor stage MF (n = 10) and benign inflammatory dermatoses (Lichen planus n = 6, Eczema n = 5) calculated by Delta Ct method. Horizontal bars represent the mean. All miRNAs are significant differentially expressed between tumor stage MF and benign inflammatory dermatoses, p‐values were measured by Mann–Whitney independent t test.