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STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma

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Harvard

Kopp, KL, Ralfkiaer, U, Gjerdrum, LMR, Helvad, R, Pedersen, IH, Litman, T, Jønson, L, Hagedorn, PH, Krejsgaard, T, Gniadecki, R, Bonefeld, CM, Skov, L, Geisler, C, Wasik, MA, Ralfkiaer, E, Ødum, N & Woetmann, A 2013, 'STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma' Cell cycle (Georgetown, Tex.), bind 12, nr. 12, s. 1939-47. https://doi.org/10.4161/cc.24987

APA

CBE

Kopp KL, Ralfkiaer U, Gjerdrum LMR, Helvad R, Pedersen IH, Litman T, Jønson L, Hagedorn PH, Krejsgaard T, Gniadecki R, Bonefeld CM, Skov L, Geisler C, Wasik MA, Ralfkiaer E, Ødum N, Woetmann A. 2013. STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma. Cell cycle (Georgetown, Tex.). 12(12):1939-47. https://doi.org/10.4161/cc.24987

MLA

Vancouver

Author

Kopp, Katharina L ; Ralfkiaer, Ulrik ; Gjerdrum, Lise Mette R ; Helvad, Rikke ; Pedersen, Ida H ; Litman, Thomas ; Jønson, Lars ; Hagedorn, Peter H ; Krejsgaard, Thorbjørn ; Gniadecki, Robert ; Bonefeld, Charlotte M ; Skov, Lone ; Geisler, Carsten ; Wasik, Mariusz A ; Ralfkiaer, Elisabeth ; Ødum, Niels ; Woetmann, Anders. / STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma. I: Cell cycle (Georgetown, Tex.). 2013 ; Bind 12, Nr. 12. s. 1939-47.

Bibtex

@article{f25e6c8d02a6431daa7f71d9db293b76,
title = "STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma",
abstract = "The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains elusive. Recent discoveries indicate that the oncogenic microRNA miR-155 is overexpressed in affected skin from CTCL patients. Here, we address what drives the expression of miR-155 and investigate its role in the pathogenesis of CTCL. We show that malignant T cells constitutively express high levels of miR-155 and its host gene BIC (B cell integration cluster). Using ChIP-seq, we identify BIC as a target of transcription factor STAT5, which is aberrantly activated in malignant T cells and induced by IL-2/IL-15 in non-malignant T cells. Incubation with JAK inhibitor or siRNA-mediated knockdown of STAT5 decreases BIC/miR-155 expression, whereas IL-2 and IL-15 increase their expression in cell lines and primary cells. In contrast, knockdown of STAT3 has no effect, and BIC is not a transcriptional target of STAT3, indicating that regulation of BIC/miR-155 expression by STAT5 is highly specific. Malignant proliferation is significantly inhibited by an antisense-miR-155 as well as by knockdown of STAT5 and BIC.   In conclusion, we provide the first evidence that STAT5 drives expression of oncogenic BIC/miR-155 in cancer. Moreover, our data indicate that the STAT5/BIC/miR-155 pathway promotes proliferation of malignant T cells, and therefore is a putative target for therapy in CTCL.",
author = "Kopp, {Katharina L} and Ulrik Ralfkiaer and Gjerdrum, {Lise Mette R} and Rikke Helvad and Pedersen, {Ida H} and Thomas Litman and Lars J{\o}nson and Hagedorn, {Peter H} and Thorbj{\o}rn Krejsgaard and Robert Gniadecki and Bonefeld, {Charlotte M} and Lone Skov and Carsten Geisler and Wasik, {Mariusz A} and Elisabeth Ralfkiaer and Niels {\O}dum and Anders Woetmann",
year = "2013",
month = "6",
day = "15",
doi = "10.4161/cc.24987",
language = "English",
volume = "12",
pages = "1939--47",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "12",

}

RIS

TY - JOUR

T1 - STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma

AU - Kopp, Katharina L

AU - Ralfkiaer, Ulrik

AU - Gjerdrum, Lise Mette R

AU - Helvad, Rikke

AU - Pedersen, Ida H

AU - Litman, Thomas

AU - Jønson, Lars

AU - Hagedorn, Peter H

AU - Krejsgaard, Thorbjørn

AU - Gniadecki, Robert

AU - Bonefeld, Charlotte M

AU - Skov, Lone

AU - Geisler, Carsten

AU - Wasik, Mariusz A

AU - Ralfkiaer, Elisabeth

AU - Ødum, Niels

AU - Woetmann, Anders

PY - 2013/6/15

Y1 - 2013/6/15

N2 - The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains elusive. Recent discoveries indicate that the oncogenic microRNA miR-155 is overexpressed in affected skin from CTCL patients. Here, we address what drives the expression of miR-155 and investigate its role in the pathogenesis of CTCL. We show that malignant T cells constitutively express high levels of miR-155 and its host gene BIC (B cell integration cluster). Using ChIP-seq, we identify BIC as a target of transcription factor STAT5, which is aberrantly activated in malignant T cells and induced by IL-2/IL-15 in non-malignant T cells. Incubation with JAK inhibitor or siRNA-mediated knockdown of STAT5 decreases BIC/miR-155 expression, whereas IL-2 and IL-15 increase their expression in cell lines and primary cells. In contrast, knockdown of STAT3 has no effect, and BIC is not a transcriptional target of STAT3, indicating that regulation of BIC/miR-155 expression by STAT5 is highly specific. Malignant proliferation is significantly inhibited by an antisense-miR-155 as well as by knockdown of STAT5 and BIC.   In conclusion, we provide the first evidence that STAT5 drives expression of oncogenic BIC/miR-155 in cancer. Moreover, our data indicate that the STAT5/BIC/miR-155 pathway promotes proliferation of malignant T cells, and therefore is a putative target for therapy in CTCL.

AB - The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains elusive. Recent discoveries indicate that the oncogenic microRNA miR-155 is overexpressed in affected skin from CTCL patients. Here, we address what drives the expression of miR-155 and investigate its role in the pathogenesis of CTCL. We show that malignant T cells constitutively express high levels of miR-155 and its host gene BIC (B cell integration cluster). Using ChIP-seq, we identify BIC as a target of transcription factor STAT5, which is aberrantly activated in malignant T cells and induced by IL-2/IL-15 in non-malignant T cells. Incubation with JAK inhibitor or siRNA-mediated knockdown of STAT5 decreases BIC/miR-155 expression, whereas IL-2 and IL-15 increase their expression in cell lines and primary cells. In contrast, knockdown of STAT3 has no effect, and BIC is not a transcriptional target of STAT3, indicating that regulation of BIC/miR-155 expression by STAT5 is highly specific. Malignant proliferation is significantly inhibited by an antisense-miR-155 as well as by knockdown of STAT5 and BIC.   In conclusion, we provide the first evidence that STAT5 drives expression of oncogenic BIC/miR-155 in cancer. Moreover, our data indicate that the STAT5/BIC/miR-155 pathway promotes proliferation of malignant T cells, and therefore is a putative target for therapy in CTCL.

U2 - 10.4161/cc.24987

DO - 10.4161/cc.24987

M3 - Journal article

VL - 12

SP - 1939

EP - 1947

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 12

ER -

ID: 38986955