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STAT5 induces miR-21 expression in cutaneous T cell lymphoma

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STAT5 induces miR-21 expression in cutaneous T cell lymphoma. / Lindahl, Lise M.; Fredholm, Simon; Joseph, Claudine Vanessa; Nielsen, Boye Schnack; Jønson, Lars; Willerslev-Olsen, Andreas; Gluud, Maria; Blümel, Edda; Petersen, David L.; Sibbesen, Nina; Hu, Tengpeng; Nastasi, Claudia; Krejsgaard, Thorbjørn; Jæhger, Ditte; Persson, Jenny L.; Mongan, Nigel; Wasik, Mariusz A.; Litvinov, Ivan V.; Sasseville, Denis; Koralov, Sergei B.; Bonefeld, Charlotte M.; Geisler, Carsten; Andersen, Anders Woetmann; Ralfkiaer, Elisabeth; Iversen, Lars; Odum, Niels.

In: OncoTarget, Vol. 7, No. 29, 2016, p. 45730-45744.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Lindahl, LM, Fredholm, S, Joseph, CV, Nielsen, BS, Jønson, L, Willerslev-Olsen, A, Gluud, M, Blümel, E, Petersen, DL, Sibbesen, N, Hu, T, Nastasi, C, Krejsgaard, T, Jæhger, D, Persson, JL, Mongan, N, Wasik, MA, Litvinov, IV, Sasseville, D, Koralov, SB, Bonefeld, CM, Geisler, C, Andersen, AW, Ralfkiaer, E, Iversen, L & Odum, N 2016, 'STAT5 induces miR-21 expression in cutaneous T cell lymphoma' OncoTarget, vol. 7, no. 29, pp. 45730-45744. https://doi.org/10.18632/oncotarget.10160

APA

Lindahl, L. M., Fredholm, S., Joseph, C. V., Nielsen, B. S., Jønson, L., Willerslev-Olsen, A., ... Odum, N. (2016). STAT5 induces miR-21 expression in cutaneous T cell lymphoma. OncoTarget, 7(29), 45730-45744. https://doi.org/10.18632/oncotarget.10160

Vancouver

Lindahl LM, Fredholm S, Joseph CV, Nielsen BS, Jønson L, Willerslev-Olsen A et al. STAT5 induces miR-21 expression in cutaneous T cell lymphoma. OncoTarget. 2016;7(29):45730-45744. https://doi.org/10.18632/oncotarget.10160

Author

Lindahl, Lise M. ; Fredholm, Simon ; Joseph, Claudine Vanessa ; Nielsen, Boye Schnack ; Jønson, Lars ; Willerslev-Olsen, Andreas ; Gluud, Maria ; Blümel, Edda ; Petersen, David L. ; Sibbesen, Nina ; Hu, Tengpeng ; Nastasi, Claudia ; Krejsgaard, Thorbjørn ; Jæhger, Ditte ; Persson, Jenny L. ; Mongan, Nigel ; Wasik, Mariusz A. ; Litvinov, Ivan V. ; Sasseville, Denis ; Koralov, Sergei B. ; Bonefeld, Charlotte M. ; Geisler, Carsten ; Andersen, Anders Woetmann ; Ralfkiaer, Elisabeth ; Iversen, Lars ; Odum, Niels. / STAT5 induces miR-21 expression in cutaneous T cell lymphoma. In: OncoTarget. 2016 ; Vol. 7, No. 29. pp. 45730-45744.

Bibtex

@article{65bf5e12eca54e338e76a5e93e5889d6,
title = "STAT5 induces miR-21 expression in cutaneous T cell lymphoma",
abstract = "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.",
keywords = "Cutaneous T-cell lymphoma (CTCL), IL-2, In situ, miR-21, STAT5",
author = "Lindahl, {Lise M.} and Simon Fredholm and Joseph, {Claudine Vanessa} and Nielsen, {Boye Schnack} and Lars J{\o}nson and Andreas Willerslev-Olsen and Maria Gluud and Edda Bl{\"u}mel and Petersen, {David L.} and Nina Sibbesen and Tengpeng Hu and Claudia Nastasi and Thorbj{\o}rn Krejsgaard and Ditte J{\ae}hger and Persson, {Jenny L.} and Nigel Mongan and Wasik, {Mariusz A.} and Litvinov, {Ivan V.} and Denis Sasseville and Koralov, {Sergei B.} and Bonefeld, {Charlotte M.} and Carsten Geisler and Andersen, {Anders Woetmann} and Elisabeth Ralfkiaer and Lars Iversen and Niels Odum",
year = "2016",
doi = "10.18632/oncotarget.10160",
language = "English",
volume = "7",
pages = "45730--45744",
journal = "OncoTarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "29",

}

RIS

TY - JOUR

T1 - STAT5 induces miR-21 expression in cutaneous T cell lymphoma

AU - Lindahl, Lise M.

AU - Fredholm, Simon

AU - Joseph, Claudine Vanessa

AU - Nielsen, Boye Schnack

AU - Jønson, Lars

AU - Willerslev-Olsen, Andreas

AU - Gluud, Maria

AU - Blümel, Edda

AU - Petersen, David L.

AU - Sibbesen, Nina

AU - Hu, Tengpeng

AU - Nastasi, Claudia

AU - Krejsgaard, Thorbjørn

AU - Jæhger, Ditte

AU - Persson, Jenny L.

AU - Mongan, Nigel

AU - Wasik, Mariusz A.

AU - Litvinov, Ivan V.

AU - Sasseville, Denis

AU - Koralov, Sergei B.

AU - Bonefeld, Charlotte M.

AU - Geisler, Carsten

AU - Andersen, Anders Woetmann

AU - Ralfkiaer, Elisabeth

AU - Iversen, Lars

AU - Odum, Niels

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Cutaneous T-cell lymphoma (CTCL)

KW - IL-2

KW - In situ

KW - miR-21

KW - STAT5

U2 - 10.18632/oncotarget.10160

DO - 10.18632/oncotarget.10160

M3 - Journal article

VL - 7

SP - 45730

EP - 45744

JO - OncoTarget

JF - OncoTarget

SN - 1949-2553

IS - 29

ER -

ID: 168874893