期刊
BLOOD
卷 116, 期 7, 页码 1105-1113出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-12-256719
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资金
- Leukemia Research Fund
- Julian Starmer-Smith Memorial Fund
- Fondation Rene Touraine
- Guys and St Thomas' National Health Service (NHS) Foundation Trust
- Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Center
- Kings College Hospital NHS Foundation Trust
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 Sezary 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. (Blood. 2010;116(7):1105-1113)
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