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

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...

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Detalles Bibliográficos
Autores: Olivan Riera, Mireia, Garcia, Marta, Suárez, Leticia, Guiu, Marc, Gros, Laura, Méndez, Olga, Rigau, Marina, Reventós Puigjaner, Jaume, Segura, Miguel F., Torres, Inés de, Planas, Jacques, Cruz, Xavier de la, Gomis i Cabré, Roger, Morote, Juan, Rodríguez Barrueco, Ruth, Santamaria Margalef, Anna
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/182321
Acceso en línea:https://hdl.handle.net/2445/182321
Access Level:acceso abierto
Palabra clave:Càncer de pròstata
Metàstasi
Marcadors bioquímics
Prostate cancer
Metastasis
Biochemical markers
Descripción
Sumario: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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