cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas. / Manfè, Valentina; Biskup, Edyta; Willumsgaard, Ayalah; Skov, Anne Guldhammer; Palmieri, Dario; Gasparini, Pierluigi; Laganá, Alessandro; Andersen, Anders Woetmann; Ødum, Niels; Croce, Carlo Maria; Gniadecki, Robert.

In: PloS one, Vol. 8, No. 3, 2013, p. e59390.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Manfè, V, Biskup, E, Willumsgaard, A, Skov, AG, Palmieri, D, Gasparini, P, Laganá, A, Andersen, AW, Ødum, N, Croce, CM & Gniadecki, R 2013, 'cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas', PloS one, vol. 8, no. 3, pp. e59390. https://doi.org/10.1371/journal.pone.0059390

APA

Manfè, V., Biskup, E., Willumsgaard, A., Skov, A. G., Palmieri, D., Gasparini, P., Laganá, A., Andersen, A. W., Ødum, N., Croce, C. M., & Gniadecki, R. (2013). cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas. PloS one, 8(3), e59390. https://doi.org/10.1371/journal.pone.0059390

Vancouver

Manfè V, Biskup E, Willumsgaard A, Skov AG, Palmieri D, Gasparini P et al. cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas. PloS one. 2013;8(3):e59390. https://doi.org/10.1371/journal.pone.0059390

Author

Manfè, Valentina ; Biskup, Edyta ; Willumsgaard, Ayalah ; Skov, Anne Guldhammer ; Palmieri, Dario ; Gasparini, Pierluigi ; Laganá, Alessandro ; Andersen, Anders Woetmann ; Ødum, Niels ; Croce, Carlo Maria ; Gniadecki, Robert. / cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas. In: PloS one. 2013 ; Vol. 8, No. 3. pp. e59390.

Bibtex

@article{90d431417fc14cf5a9d42f6fae0a688f,
title = "cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas",
abstract = "Successful/effective cancer therapy in low grade lymphoma is often hampered by cell resistance to anti-neoplastic agents. The crucial mechanisms responsible for this phenomenon are poorly understood. Overcoming resistance of tumor cells to anticancer agents, such as proteasome inhibitors, could improve their clinical efficacy. Using cutaneous T-cell lymphoma (CTCL) as a model of the chemotherapy-resistant peripheral lymphoid malignancy, we demonstrated that resistance to proteasome inhibition involved a signaling between the oncogene cMyc and miR-125b-5p. Bortezomib repressed cMyc and simultaneously induced miR-125b-5p that exerted a cytoprotective effect through the downmodulation of MAD4. Overexpression of cMyc repressed miR-125b-5p transcription and sensitized lymphoma cells to bortezomib. The central role of miR-125b-5p was further confirmed in a mouse model of T-cell lymphoma, where xenotransplantation of human CTCL cells overexpressing miR-125b-5p resulted in enhanced tumor growth and a shorter median survival. Our findings describe a novel mechanism through which miR-125b-5p not only regulates tumor growth in vivo, but also increases cellular resistance to proteasome inhibitors via modulation of MAD4.",
keywords = "Animals, Basic Helix-Loop-Helix Transcription Factors, Blotting, Western, Boronic Acids, Chromatin Immunoprecipitation, Computational Biology, DNA Primers, Drug Resistance, Neoplasm, Humans, Immunohistochemistry, In Situ Hybridization, Kaplan-Meier Estimate, Luciferases, Lymphoma, T-Cell, Mice, MicroRNAs, Proteasome Inhibitors, Proto-Oncogene Proteins c-myc, Pyrazines, RNA, Small Interfering, Repressor Proteins, Signal Transduction, Skin Neoplasms",
author = "Valentina Manf{\`e} and Edyta Biskup and Ayalah Willumsgaard and Skov, {Anne Guldhammer} and Dario Palmieri and Pierluigi Gasparini and Alessandro Lagan{\'a} and Andersen, {Anders Woetmann} and Niels {\O}dum and Croce, {Carlo Maria} and Robert Gniadecki",
year = "2013",
doi = "10.1371/journal.pone.0059390",
language = "English",
volume = "8",
pages = "e59390",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

RIS

TY - JOUR

T1 - cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas

AU - Manfè, Valentina

AU - Biskup, Edyta

AU - Willumsgaard, Ayalah

AU - Skov, Anne Guldhammer

AU - Palmieri, Dario

AU - Gasparini, Pierluigi

AU - Laganá, Alessandro

AU - Andersen, Anders Woetmann

AU - Ødum, Niels

AU - Croce, Carlo Maria

AU - Gniadecki, Robert

PY - 2013

Y1 - 2013

N2 - Successful/effective cancer therapy in low grade lymphoma is often hampered by cell resistance to anti-neoplastic agents. The crucial mechanisms responsible for this phenomenon are poorly understood. Overcoming resistance of tumor cells to anticancer agents, such as proteasome inhibitors, could improve their clinical efficacy. Using cutaneous T-cell lymphoma (CTCL) as a model of the chemotherapy-resistant peripheral lymphoid malignancy, we demonstrated that resistance to proteasome inhibition involved a signaling between the oncogene cMyc and miR-125b-5p. Bortezomib repressed cMyc and simultaneously induced miR-125b-5p that exerted a cytoprotective effect through the downmodulation of MAD4. Overexpression of cMyc repressed miR-125b-5p transcription and sensitized lymphoma cells to bortezomib. The central role of miR-125b-5p was further confirmed in a mouse model of T-cell lymphoma, where xenotransplantation of human CTCL cells overexpressing miR-125b-5p resulted in enhanced tumor growth and a shorter median survival. Our findings describe a novel mechanism through which miR-125b-5p not only regulates tumor growth in vivo, but also increases cellular resistance to proteasome inhibitors via modulation of MAD4.

AB - Successful/effective cancer therapy in low grade lymphoma is often hampered by cell resistance to anti-neoplastic agents. The crucial mechanisms responsible for this phenomenon are poorly understood. Overcoming resistance of tumor cells to anticancer agents, such as proteasome inhibitors, could improve their clinical efficacy. Using cutaneous T-cell lymphoma (CTCL) as a model of the chemotherapy-resistant peripheral lymphoid malignancy, we demonstrated that resistance to proteasome inhibition involved a signaling between the oncogene cMyc and miR-125b-5p. Bortezomib repressed cMyc and simultaneously induced miR-125b-5p that exerted a cytoprotective effect through the downmodulation of MAD4. Overexpression of cMyc repressed miR-125b-5p transcription and sensitized lymphoma cells to bortezomib. The central role of miR-125b-5p was further confirmed in a mouse model of T-cell lymphoma, where xenotransplantation of human CTCL cells overexpressing miR-125b-5p resulted in enhanced tumor growth and a shorter median survival. Our findings describe a novel mechanism through which miR-125b-5p not only regulates tumor growth in vivo, but also increases cellular resistance to proteasome inhibitors via modulation of MAD4.

KW - Animals

KW - Basic Helix-Loop-Helix Transcription Factors

KW - Blotting, Western

KW - Boronic Acids

KW - Chromatin Immunoprecipitation

KW - Computational Biology

KW - DNA Primers

KW - Drug Resistance, Neoplasm

KW - Humans

KW - Immunohistochemistry

KW - In Situ Hybridization

KW - Kaplan-Meier Estimate

KW - Luciferases

KW - Lymphoma, T-Cell

KW - Mice

KW - MicroRNAs

KW - Proteasome Inhibitors

KW - Proto-Oncogene Proteins c-myc

KW - Pyrazines

KW - RNA, Small Interfering

KW - Repressor Proteins

KW - Signal Transduction

KW - Skin Neoplasms

U2 - 10.1371/journal.pone.0059390

DO - 10.1371/journal.pone.0059390

M3 - Journal article

C2 - 23527180

VL - 8

SP - e59390

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 3

ER -

ID: 117552020