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...
| Autores: | , , , , , , , , , , , , , , , |
|---|---|
| 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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| 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 |
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info:eu-repo/semantics/article |
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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 |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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Universitat Autònoma de Barcelona |
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Dipòsit Digital de Documents de la UAB |
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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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15,198674 |