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

Simple Summary 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...

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Autores: Olivan M, Garcia M, Suárez L, Guiu M, Gros L, Méndez O, Rigau M, Reventós J, Segura MF, de Torres I, Planas J, de la Cruz X, Gomis RR, Morote J, Rodríguez-Barrueco R, Santamaria A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p20467
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=20467
Access Level:acceso abierto
Palabra clave:miRNA-135b
prostate cancer
bone metastasis
miRNAs
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spelling Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate SamplesOlivan MGarcia MSuárez LGuiu MGros LMéndez ORigau MReventós JSegura MFde Torres IPlanas Jde la Cruz XGomis RRMorote JRodríguez-Barrueco RSantamaria AmiRNA-135bprostate cancerbone metastasismiRNAsSimple Summary 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.MDPI2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=20467CancersISSN: 20726694reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p204672026-05-27T12:37:41Z
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 M
miRNA-135b
prostate cancer
bone metastasis
miRNAs
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 M
Garcia M
Suárez L
Guiu M
Gros L
Méndez O
Rigau M
Reventós J
Segura MF
de Torres I
Planas J
de la Cruz X
Gomis RR
Morote J
Rodríguez-Barrueco R
Santamaria A
author Olivan M
author_facet Olivan M
Garcia M
Suárez L
Guiu M
Gros L
Méndez O
Rigau M
Reventós J
Segura MF
de Torres I
Planas J
de la Cruz X
Gomis RR
Morote J
Rodríguez-Barrueco R
Santamaria A
author_role author
author2 Garcia M
Suárez L
Guiu M
Gros L
Méndez O
Rigau M
Reventós J
Segura MF
de Torres I
Planas J
de la Cruz X
Gomis RR
Morote J
Rodríguez-Barrueco R
Santamaria A
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv miRNA-135b
prostate cancer
bone metastasis
miRNAs
topic miRNA-135b
prostate cancer
bone metastasis
miRNAs
description Simple Summary 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 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=20467
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=20467
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Cancers
ISSN: 20726694
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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