Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples
| Autor: | Mireia Olivan, Marta Garcia, Leticia Suárez, Marc Guiu, Laura Gros, Olga Méndez, Marina Rigau, Jaume Reventós, Miguel F. Segura, Inés de Torres, Jacques Planas, Xavier de la Cruz, Roger R. Gomis, Juan Morote, Ruth Rodríguez-Barrueco, Anna Santamaria |
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| Přispěvatelé: | Institut Català de la Salut, [Olivan M] Translational Oncology Laboratory, Anatomy Unit, Department of Pathology and Experimental Therapy, School of Medicine, Universitat de Barcelona (UB), 08907 L’Hospitalet de Llobregat, Spain. Molecular Mechanisms and Experimental Therapy in Oncology-Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), 08908 L’Hospitalet de Llobregat, Spain. Laboratori de Cicle Cel•lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Garcia M] Laboratori de Cicle Cel•lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Developmental Tumor Biology Laboratory, Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain. [Suárez L, Gros L, Méndez O, Santamaria A] Laboratori de Cicle Cel•lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Guiu M] Cancer Science Programme, Institute for Research in Biomedicine (IRB-Barcelona), 08028 Barcelona, Spain. [Segura MF] Grup de Recerca Translacional en Càncer en la Infància i l’Adolescència, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [de Torres I] Laboratori de Cicle Cel•lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Planas J, Morote J] Laboratori de Cicle Cel•lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei d’Urologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [de la Cruz X] Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain. Grup de Recerca en Bioinformàtica Clínica i Translacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
MicroARN miRNA-135b prostate cancer bone metastasis miRNAs Prostate cancer Càncer de pròstata Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms Male::Prostatic Neoplasms [DISEASES] Biochemical markers Neoplasms::Neoplastic Processes::Neoplasm Metastasis [DISEASES] Neoplasms. Tumors. Oncology. Including cancer and carcinogens urologic and male genital diseases Article Metastasis neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata [ENFERMEDADES] Oncology Metàstasi neoplasias::procesos neoplásicos::metástasis neoplásica [ENFERMEDADES] Marcadors bioquímics Pròstata - Càncer - Prognosi Diagnosis::Prognosis [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] diagnóstico::pronóstico [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] RC254-282 |
| Zdroj: | Scientia Cancers, Vol 13, Iss 6202, p 6202 (2021) Dipòsit Digital de la UB Universidad de Barcelona Cancers; Volume 13; Issue 24; Pages: 6202 Cancers |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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