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STAT5 induces miR-21 expression in cutaneous T cell lymphoma


Lise M. Lindahl

Simon Fredholm

Claudine Joseph

Boye Schnack Nielsen


Andreas Willerslev-Olsen

Maria Gluud


David L. Petersen

Nina Sibbesen

Tengpeng Hu

Claudia Nastasi



Jenny L. Persson

Nigel P. Mongan

Mariusz A. Wasik

Ivan V. Litvinov

Denis Sasseville

Sergei B. Koralov

Charlotte M. Bonefeld

Carsten Geisler

Anders Woetmann

Elisabeth Ralfkiaer

Lars Iversen

Niels Odum


In cutaneous T cell lymphomas (CTCL), miR-21 is aberrantly expressed in skin and peripheral blood and displays anti-apoptotic properties in malignant T cells. It is, however, unclear exactly which cells express miR-21 and what mechanisms regulate miR-21. Here, we demonstrate miR-21 expression in situ in both malignant and reactive lymphocytes as well as stromal cells. qRT-PCR analysis of 47 patients with mycosis fungoides (MF) and Sezary Syndrome (SS) confirmed an increased miR-21 expression that correlated with progressive disease. In cultured malignant T cells miR-21 expression was inhibited by Tofacitinib (CP-690550), a clinical-grade JAK3 inhibitor. Chromatin immunoprecipitation (ChIP) analysis showed direct binding of STAT5 to the miR-21 promoter. Cytokine starvation ex vivo triggered a decrease in miR-21 expression, whereas IL-2 induced an increased miR-21 expression in primary SS T cells and cultured cytokine-dependent SS cells (SeAx). siRNA-mediated depletion of STAT5 inhibited constitutive- and IL-2-induced miR-21 expression in cytokine-independent and dependent T cell lines, respectively. IL-15 and IL-2 were more potent than IL-21 in inducing miR-21 expression in the cytokine-dependent T cells. In conclusion, we provide first evidence that miR-21 is expressed in situ in CTCL skin lesions, induced by IL-2 and IL-15 cytokines, and is regulated by STAT5 in malignant T cells. Thus, our data provide novel evidence for a pathological role of IL-2Rg cytokines in promoting expression of the oncogenic miR-21 in CTCL.


Lindahl, L. M., Fredholm, S., Joseph, C., Nielsen, B. S., Jønson, L., Willerslev-Olsen, A., …Odum, N. (2016). STAT5 induces miR-21 expression in cutaneous T cell lymphoma. Oncotarget,

Journal Article Type Article
Acceptance Date Jun 3, 2016
Publication Date Jun 18, 2016
Deposit Date Sep 15, 2016
Publicly Available Date Sep 15, 2016
Journal Oncotarget
Electronic ISSN 1949-2553
Publisher Impact Journals
Peer Reviewed Peer Reviewed
Keywords MiR-21, in situ, STAT5, IL-2, Cutaneous T-cell lymphoma (CTCL)
Public URL
Publisher URL


2016_Oncotarget_miR21.pdf (3.5 Mb)

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