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Menin inhibition suppresses castration-resistant prostate cancer and enhances chemosensitivity

Disease progression and therapeutic resistance of prostate cancer (PC) are linked to multiple molecular events that promote survival and plasticity. We previously showed that heat shock protein 27 (HSP27) acted as a driver of castration-resistant phenotype (CRPC) and developed an oligonucleotides an...

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Autores principales: Cherif, Chaïma, Nguyen, Dang Tan, Paris, Clément, Le, Thi Khanh, Sefiane, Thibaud, Carbuccia, Nadine, Finetti, Pascal, Chaffanet, Max, kaoutari, Abdessamad El, Vernerey, Julien, Fazli, Ladan, Gleave, Martin, Manai, Mohamed, Barthélémy, Philippe, Birnbaum, Daniel, Bertucci, François, Taïeb, David, Rocchi, Palma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724010/
https://www.ncbi.nlm.nih.gov/pubmed/34711954
http://dx.doi.org/10.1038/s41388-021-02039-2
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author Cherif, Chaïma
Nguyen, Dang Tan
Paris, Clément
Le, Thi Khanh
Sefiane, Thibaud
Carbuccia, Nadine
Finetti, Pascal
Chaffanet, Max
kaoutari, Abdessamad El
Vernerey, Julien
Fazli, Ladan
Gleave, Martin
Manai, Mohamed
Barthélémy, Philippe
Birnbaum, Daniel
Bertucci, François
Taïeb, David
Rocchi, Palma
author_facet Cherif, Chaïma
Nguyen, Dang Tan
Paris, Clément
Le, Thi Khanh
Sefiane, Thibaud
Carbuccia, Nadine
Finetti, Pascal
Chaffanet, Max
kaoutari, Abdessamad El
Vernerey, Julien
Fazli, Ladan
Gleave, Martin
Manai, Mohamed
Barthélémy, Philippe
Birnbaum, Daniel
Bertucci, François
Taïeb, David
Rocchi, Palma
author_sort Cherif, Chaïma
collection PubMed
description Disease progression and therapeutic resistance of prostate cancer (PC) are linked to multiple molecular events that promote survival and plasticity. We previously showed that heat shock protein 27 (HSP27) acted as a driver of castration-resistant phenotype (CRPC) and developed an oligonucleotides antisense (ASO) against HSP27 with evidence of anti-cancer activity in men with CRPC. Here, we show that the tumor suppressor Menin (MEN1) is highly regulated by HSP27. Menin is overexpressed in high-grade PC and CRPC. High MEN1 mRNA expression is associated with decreased biochemical relapse-free and overall survival. Silencing Menin with ASO technology inhibits CRPC cell proliferation, tumor growth, and restores chemotherapeutic sensitivity. ChIP-seq analysis revealed differential DNA binding sites of Menin in various prostatic cells, suggesting a switch from tumor suppressor to oncogenic functions in CRPC. These data support the evaluation of ASO against Menin for CRPC.
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spelling pubmed-87240102022-01-18 Menin inhibition suppresses castration-resistant prostate cancer and enhances chemosensitivity Cherif, Chaïma Nguyen, Dang Tan Paris, Clément Le, Thi Khanh Sefiane, Thibaud Carbuccia, Nadine Finetti, Pascal Chaffanet, Max kaoutari, Abdessamad El Vernerey, Julien Fazli, Ladan Gleave, Martin Manai, Mohamed Barthélémy, Philippe Birnbaum, Daniel Bertucci, François Taïeb, David Rocchi, Palma Oncogene Article Disease progression and therapeutic resistance of prostate cancer (PC) are linked to multiple molecular events that promote survival and plasticity. We previously showed that heat shock protein 27 (HSP27) acted as a driver of castration-resistant phenotype (CRPC) and developed an oligonucleotides antisense (ASO) against HSP27 with evidence of anti-cancer activity in men with CRPC. Here, we show that the tumor suppressor Menin (MEN1) is highly regulated by HSP27. Menin is overexpressed in high-grade PC and CRPC. High MEN1 mRNA expression is associated with decreased biochemical relapse-free and overall survival. Silencing Menin with ASO technology inhibits CRPC cell proliferation, tumor growth, and restores chemotherapeutic sensitivity. ChIP-seq analysis revealed differential DNA binding sites of Menin in various prostatic cells, suggesting a switch from tumor suppressor to oncogenic functions in CRPC. These data support the evaluation of ASO against Menin for CRPC. Nature Publishing Group UK 2021-10-28 2022 /pmc/articles/PMC8724010/ /pubmed/34711954 http://dx.doi.org/10.1038/s41388-021-02039-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Cherif, Chaïma
Nguyen, Dang Tan
Paris, Clément
Le, Thi Khanh
Sefiane, Thibaud
Carbuccia, Nadine
Finetti, Pascal
Chaffanet, Max
kaoutari, Abdessamad El
Vernerey, Julien
Fazli, Ladan
Gleave, Martin
Manai, Mohamed
Barthélémy, Philippe
Birnbaum, Daniel
Bertucci, François
Taïeb, David
Rocchi, Palma
Menin inhibition suppresses castration-resistant prostate cancer and enhances chemosensitivity
title Menin inhibition suppresses castration-resistant prostate cancer and enhances chemosensitivity
title_full Menin inhibition suppresses castration-resistant prostate cancer and enhances chemosensitivity
title_fullStr Menin inhibition suppresses castration-resistant prostate cancer and enhances chemosensitivity
title_full_unstemmed Menin inhibition suppresses castration-resistant prostate cancer and enhances chemosensitivity
title_short Menin inhibition suppresses castration-resistant prostate cancer and enhances chemosensitivity
title_sort menin inhibition suppresses castration-resistant prostate cancer and enhances chemosensitivity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724010/
https://www.ncbi.nlm.nih.gov/pubmed/34711954
http://dx.doi.org/10.1038/s41388-021-02039-2
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