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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 patient...

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Autores principales: Olivan, Mireia, Garcia, Marta, Suárez, Leticia, Guiu, Marc, Gros, Laura, Méndez, Olga, Rigau, Marina, Reventós, Jaume, Segura, Miguel F., de Torres, Inés, Planas, Jacques, de la Cruz, Xavier, Gomis, Roger R., Morote, Juan, Rodríguez-Barrueco, Ruth, Santamaria, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699528/
https://www.ncbi.nlm.nih.gov/pubmed/34944822
http://dx.doi.org/10.3390/cancers13246202
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author Olivan, Mireia
Garcia, Marta
Suárez, Leticia
Guiu, Marc
Gros, Laura
Méndez, Olga
Rigau, Marina
Reventós, Jaume
Segura, Miguel F.
de Torres, Inés
Planas, Jacques
de la Cruz, Xavier
Gomis, Roger R.
Morote, Juan
Rodríguez-Barrueco, Ruth
Santamaria, Anna
author_facet Olivan, Mireia
Garcia, Marta
Suárez, Leticia
Guiu, Marc
Gros, Laura
Méndez, Olga
Rigau, Marina
Reventós, Jaume
Segura, Miguel F.
de Torres, Inés
Planas, Jacques
de la Cruz, Xavier
Gomis, Roger R.
Morote, Juan
Rodríguez-Barrueco, Ruth
Santamaria, Anna
author_sort Olivan, Mireia
collection PubMed
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. ABSTRACT: 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.
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spelling pubmed-86995282021-12-24 Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples Olivan, Mireia Garcia, Marta Suárez, Leticia Guiu, Marc Gros, Laura Méndez, Olga Rigau, Marina Reventós, Jaume Segura, Miguel F. de Torres, Inés Planas, Jacques de la Cruz, Xavier Gomis, Roger R. Morote, Juan Rodríguez-Barrueco, Ruth Santamaria, Anna Cancers (Basel) Article 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. ABSTRACT: 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. MDPI 2021-12-09 /pmc/articles/PMC8699528/ /pubmed/34944822 http://dx.doi.org/10.3390/cancers13246202 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Olivan, Mireia
Garcia, Marta
Suárez, Leticia
Guiu, Marc
Gros, Laura
Méndez, Olga
Rigau, Marina
Reventós, Jaume
Segura, Miguel F.
de Torres, Inés
Planas, Jacques
de la Cruz, Xavier
Gomis, Roger R.
Morote, Juan
Rodríguez-Barrueco, Ruth
Santamaria, Anna
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
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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699528/
https://www.ncbi.nlm.nih.gov/pubmed/34944822
http://dx.doi.org/10.3390/cancers13246202
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