Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples

Prostate cancer (PCa) is the most prevalent cancer in males worldwide, and it was the fifth leading cause of cancer mortality in this group in 2020. Near 70% of advanced-stage PCa patients will undergo bone metastasis, suffering pathological complications that severely affect patients' quality...

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Autores: Olivan, Mireia|||0000-0002-8464-0827, García, Marta, Suárez, Leticia|||0000-0002-3864-4616, Guiu, Marc|||0000-0002-7083-986X, Gros, Laura, Méndez Fernández, Olga, Rigau, Marina|||0000-0002-1691-454X, Reventós, Jaume, Segura, Miguel F.|||0000-0003-0916-3618, de Torres, Inés|||0000-0002-5495-9140, Planas, Jacques|||0000-0002-0222-584X, de la Cruz, Xavier|||0000-0002-9738-8472, Gomis, Roger R..|||0000-0001-6473-2858, Morote Robles, Juan|||0000-0002-2168-323X, Rodríguez-Barrueco, Ruth|||0000-0003-4925-8865, Santamaría Margalef, Anna|||0000-0001-6726-8990
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:282521
Acceso en línea:https://ddd.uab.cat/record/282521
https://dx.doi.org/urn:doi:10.3390/cancers13246202
Access Level:acceso abierto
Palabra clave:Bone metastasis
MiRNAs
MiRNA-135b
Prostate cancer
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oai_identifier_str oai:ddd.uab.cat:282521
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples
title Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples
spellingShingle Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples
Olivan, Mireia|||0000-0002-8464-0827
Bone metastasis
MiRNAs
MiRNA-135b
Prostate cancer
title_short Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples
title_full Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples
title_fullStr Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples
title_full_unstemmed Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples
title_sort Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples
dc.creator.none.fl_str_mv Olivan, Mireia|||0000-0002-8464-0827
García, Marta
Suárez, Leticia|||0000-0002-3864-4616
Guiu, Marc|||0000-0002-7083-986X
Gros, Laura
Méndez Fernández, Olga
Rigau, Marina|||0000-0002-1691-454X
Reventós, Jaume
Segura, Miguel F.|||0000-0003-0916-3618
de Torres, Inés|||0000-0002-5495-9140
Planas, Jacques|||0000-0002-0222-584X
de la Cruz, Xavier|||0000-0002-9738-8472
Gomis, Roger R..|||0000-0001-6473-2858
Morote Robles, Juan|||0000-0002-2168-323X
Rodríguez-Barrueco, Ruth|||0000-0003-4925-8865
Santamaría Margalef, Anna|||0000-0001-6726-8990
author Olivan, Mireia|||0000-0002-8464-0827
author_facet Olivan, Mireia|||0000-0002-8464-0827
García, Marta
Suárez, Leticia|||0000-0002-3864-4616
Guiu, Marc|||0000-0002-7083-986X
Gros, Laura
Méndez Fernández, Olga
Rigau, Marina|||0000-0002-1691-454X
Reventós, Jaume
Segura, Miguel F.|||0000-0003-0916-3618
de Torres, Inés|||0000-0002-5495-9140
Planas, Jacques|||0000-0002-0222-584X
de la Cruz, Xavier|||0000-0002-9738-8472
Gomis, Roger R..|||0000-0001-6473-2858
Morote Robles, Juan|||0000-0002-2168-323X
Rodríguez-Barrueco, Ruth|||0000-0003-4925-8865
Santamaría Margalef, Anna|||0000-0001-6726-8990
author_role author
author2 García, Marta
Suárez, Leticia|||0000-0002-3864-4616
Guiu, Marc|||0000-0002-7083-986X
Gros, Laura
Méndez Fernández, Olga
Rigau, Marina|||0000-0002-1691-454X
Reventós, Jaume
Segura, Miguel F.|||0000-0003-0916-3618
de Torres, Inés|||0000-0002-5495-9140
Planas, Jacques|||0000-0002-0222-584X
de la Cruz, Xavier|||0000-0002-9738-8472
Gomis, Roger R..|||0000-0001-6473-2858
Morote Robles, Juan|||0000-0002-2168-323X
Rodríguez-Barrueco, Ruth|||0000-0003-4925-8865
Santamaría Margalef, Anna|||0000-0001-6726-8990
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Bone metastasis
MiRNAs
MiRNA-135b
Prostate cancer
topic Bone metastasis
MiRNAs
MiRNA-135b
Prostate cancer
description Prostate cancer (PCa) is the most prevalent cancer in males worldwide, and it was the fifth leading cause of cancer mortality in this group in 2020. Near 70% of advanced-stage PCa patients will undergo bone metastasis, suffering pathological complications that severely affect patients' quality of life and probably progress in most cases to lethal PCa. Our main objective was to unveil novel molecules associated with choosing the bone as a metastatic niche. For this purpose, we generated and characterized a cell line with increased tropism to bone. Its molecular analysis has led us to identify factors with a potential role in bone metastasis that could also be used as biomarkers of disease progression. These data help us to understand the mechanisms that increase bone metastasis penetrance of PCa cells and could provide new therapeutic tools in the future for patients with worse prognoses. About 70% of advanced-stage prostate cancer (PCa) patients will experience bone metastasis, which severely affects patients' quality of life and progresses to lethal PCa in most cases. Hence, understanding the molecular heterogeneity of PCa cell populations and the signaling pathways associated with bone tropism is crucial. For this purpose, we generated an animal model with high penetrance to metastasize to bone using an intracardiac percutaneous injection of PC3 cells to identify PCa metastasis-promoting factors. Using genomic high-throughput analysis we identified a miRNA signature involved in bone metastasis that also presents potential as a biomarker of PCa progression in human samples. In particular, the downregulation of miR-135b favored the incidence of bone metastases by significantly increasing PCa cells' migratory capacity. Moreover, the PLAG1, JAKMIP2, PDGFA, and VTI1b target genes were identified as potential mediators of miR-135b's role in the dissemination to bone. In this study, we provide a genomic signature involved in PCa bone growth, contributing to a better understanding of the mechanisms responsible for this process. In the future, our results could ultimately translate into promising new therapeutic targets for the treatment of lethal PCa.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/282521
https://dx.doi.org/urn:doi:10.3390/cancers13246202
url https://ddd.uab.cat/record/282521
https://dx.doi.org/urn:doi:10.3390/cancers13246202
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/01017
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/02248
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI13/00173
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CD12/00475
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12/0036/0035
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
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https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate SamplesOlivan, Mireia|||0000-0002-8464-0827García, MartaSuárez, Leticia|||0000-0002-3864-4616Guiu, Marc|||0000-0002-7083-986XGros, LauraMéndez Fernández, OlgaRigau, Marina|||0000-0002-1691-454XReventós, JaumeSegura, Miguel F.|||0000-0003-0916-3618de Torres, Inés|||0000-0002-5495-9140Planas, Jacques|||0000-0002-0222-584Xde la Cruz, Xavier|||0000-0002-9738-8472Gomis, Roger R..|||0000-0001-6473-2858Morote Robles, Juan|||0000-0002-2168-323XRodríguez-Barrueco, Ruth|||0000-0003-4925-8865Santamaría Margalef, Anna|||0000-0001-6726-8990Bone metastasisMiRNAsMiRNA-135bProstate cancerProstate cancer (PCa) is the most prevalent cancer in males worldwide, and it was the fifth leading cause of cancer mortality in this group in 2020. Near 70% of advanced-stage PCa patients will undergo bone metastasis, suffering pathological complications that severely affect patients' quality of life and probably progress in most cases to lethal PCa. Our main objective was to unveil novel molecules associated with choosing the bone as a metastatic niche. For this purpose, we generated and characterized a cell line with increased tropism to bone. Its molecular analysis has led us to identify factors with a potential role in bone metastasis that could also be used as biomarkers of disease progression. These data help us to understand the mechanisms that increase bone metastasis penetrance of PCa cells and could provide new therapeutic tools in the future for patients with worse prognoses. About 70% of advanced-stage prostate cancer (PCa) patients will experience bone metastasis, which severely affects patients' quality of life and progresses to lethal PCa in most cases. Hence, understanding the molecular heterogeneity of PCa cell populations and the signaling pathways associated with bone tropism is crucial. For this purpose, we generated an animal model with high penetrance to metastasize to bone using an intracardiac percutaneous injection of PC3 cells to identify PCa metastasis-promoting factors. Using genomic high-throughput analysis we identified a miRNA signature involved in bone metastasis that also presents potential as a biomarker of PCa progression in human samples. In particular, the downregulation of miR-135b favored the incidence of bone metastases by significantly increasing PCa cells' migratory capacity. Moreover, the PLAG1, JAKMIP2, PDGFA, and VTI1b target genes were identified as potential mediators of miR-135b's role in the dissemination to bone. In this study, we provide a genomic signature involved in PCa bone growth, contributing to a better understanding of the mechanisms responsible for this process. In the future, our results could ultimately translate into promising new therapeutic targets for the treatment of lethal PCa.Universitat Autònoma de Barcelona 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/282521https://dx.doi.org/urn:doi:10.3390/cancers13246202reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/01017Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/02248Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI13/00173Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CD12/00475Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12/0036/0035open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2825212026-06-06T12:50:31Z
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