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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.

Original publication

DOI

10.1182/blood-2009-12-256719

Type

Journal article

Journal

Blood

Publication Date

19/08/2010

Volume

116

Pages

1105 - 1113

Keywords

Apoptosis, Biomarkers, Tumor, Blotting, Western, Cell Proliferation, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Luciferases, Lymphoma, B-Cell, MicroRNAs, Mycosis Fungoides, Oligonucleotide Array Sequence Analysis, Prognosis, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Sezary Syndrome, T-Lymphocytes