MicroRNA expression in Sezary syndrome: identification, function, and diagnostic potential.

Journal article

MicroRNAs are commonly aberrantly expressed in many cancers. Very little is known of their role in T-cell lymphoma, however. We therefore elucidated the complete miRNome of purified T cells from 21 patients diagnosed with Sézary Syndrome (SzS), a rare aggressive primary cutaneous T-cell (CD4(+)) lymphoma. Unsupervised cluster analysis of microarray data revealed that the microRNA expression profile was distinct from CD4(+) T-cell controls and B-cell lymphomas. The majority (104 of 114) of SzS-associated microRNAs (P < .05) were down-regulated and their expression pattern was largely consistent with previously reported genomic copy number abnormalities and were found to be highly enriched (P < .001) for aberrantly expressed target genes. Levels of miR-223 distinguished SzS samples (n = 32) from healthy controls (n = 19) and patients with mycosis fungoides (n = 11) in more than 90% of samples. Furthermore, we demonstrate that the down-regulation of intronically encoded miR-342 plays a role in the pathogenesis of SzS by inhibiting apoptosis, and describe a novel mechanism of regulation for this microRNA via binding of miR-199a* to its host gene. We also provide the first in vivo evidence for down-regulation of the miR-17-92 cluster in malignancy and demonstrate that ectopic miR-17-5p expression increases apoptosis and decreases cell proliferation in SzS cells.

Authors: Ballabio, E; Mitchell, T; van Kester, MS; Taylor, S; Dunlop, H

• Publication status: Published
• Journal: Blood
• Volume: 116
• Issue: 7
• Pages: 1105-1113
• Publication date: 2010-08-01
• DOI: 10.1182/blood-2009-12-256719
• EISSN: 1528-0020
• ISSN: 0006-4971
• Language: English
• Keywords: MicroRNAs; Prognosis; Apoptosis; Lymphoma, B-Cell; RNA, Messenger; Humans; Mycosis Fungoides; Luciferases; Reverse Transcriptase Polymerase Chain Reaction; Cell Proliferation; Gene Expression Profiling; Sezary Syndrome; Oligonucleotide Array Sequence Analysis; Gene Expression Regulation, Neoplastic; Blotting, Western; Tumor Markers, Biological; T-Lymphocytes