MicroRNA expression in Sezary syndrome: identification, function, and diagnostic potential.
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.
Ballabio
Erica
E
Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Mitchell
Tracey
T
van Kester
Marloes S
MS
Taylor
Stephen
S
Dunlop
Heather M
HM
Chi
Jianxiang
J
Tosi
Isabella
I
Vermeer
Maarten H
MH
Tramonti
Daniela
D
Saunders
Nigel J
NJ
Boultwood
Jacqueline
J
Wainscoat
James S
JS
Pezzella
Francesco
F
Whittaker
Sean J
SJ
Tensen
Cornelius P
CP
Hatton
Christian S R
CS
Lawrie
Charles H
CH
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009182:Mycosis Fungoides / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012751:Sezary Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism
D014408:Biomarkers, Tumor; C546176:MIRN342 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C531408:mirn199 microRNA, human; D008156:Luciferases
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