Skip to main content

Research Repository

Advanced Search

Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma


Nina A. Sibbesen

Katharina L. Kopp

Ivan V. Litvinov


Andreas Willerslev-Olsen

Simon Fredholm

David L. Petersen

Claudia Nastasi


Lise M. Lindahl

Robert Gniadecki

Nigel P. Mongan

Denis Sasseville

Mariusz A. Wasik

Lars Iversen

Charlotte M. Bonefeld

Carsten Geisler

Anders Woetmann

Niels Odum


Aberrant activation of Janus kinase-3 (Jak3) and its key down-stream effectors, Signal Transducer and Activator of Transcription-3 (STAT3) and STAT5, is a key feature of malignant transformation in cutaneous T-cell lymphoma (CTCL). However, it remains only partially understood how Jak3/STAT activation promotes lymphomagenesis. Recently, non-coding microRNAs (miRNAs) have been implicated in the pathogenesis of this malignancy. Here, we show that (i) malignant T cells display a decreased expression of a tumor suppressor miRNA, miR-22, when compared to non-malignant T cells, (ii) STAT5 binds the promoter of the miR-22 host gene, and (iii) inhibition of Jak3, STAT3, and STAT5 triggers increased expression of pri-miR-22 and miR-22. Curcumin, a nutrient with anti-Jak3 activity and histone deacetylase inhibitors (HDACi) also trigger increased expression of pri-miR-22 and miR-22. Transfection of malignant T cells with recombinant miR-22 inhibits the expression of validated miR-22 targets including NCoA1, a transcriptional co-activator in others cancers, as well as HDAC6, MAX, MYCBP, PTEN, and CDK2, which have all been implicated in CTCL pathogenesis. In conclusion, we provide the first evidence that de-regulated Jak3/STAT3/STAT5 signalling in CTCL cells represses the expression of the gene encoding miR-22, a novel tumor suppressor miRNA.


Sibbesen, N. A., Kopp, K. L., Litvinov, I. V., Jønson, L., Willerslev-Olsen, A., Fredholm, S., …Odum, N. (2015). Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma. Oncotarget, 6(24),

Journal Article Type Article
Publication Date Aug 21, 2015
Deposit Date Jan 15, 2016
Publicly Available Date Jan 15, 2016
Journal Oncotarget
Electronic ISSN 1949-2553
Publisher Impact Journals
Peer Reviewed Peer Reviewed
Volume 6
Issue 24
Public URL
Publisher URL[]=4111&path[]=8998


2015_Oncotarget.pdf (3 Mb)

Copyright Statement
Copyright information regarding this work can be found at the following address:

You might also like

Downloadable Citations