Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples
Por:
Olivan M, Garcia-López 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 and Santamaria A
Publicada:
1 dic 2021
Ahead of Print:
9 dic 2021
Resumen:
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.
Filiaciones:
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
Cell Cycle and Cancer Laboratory, Biomedical Research Group in Urology, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain
Garcia-López M:
Cell Cycle and Cancer Laboratory, Biomedical Research Group in Urology, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain
Developmental Tumor Biology Laboratory, Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain
Suárez L:
Cell Cycle and Cancer Laboratory, Biomedical Research Group in Urology, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain
Guiu M:
Cancer Science Programme, Institute for Research in Biomedicine (IRB-Barcelona), 08028 Barcelona, Spain
Gros L:
Cell Cycle and Cancer Laboratory, Biomedical Research Group in Urology, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain
Méndez O:
Cell Cycle and Cancer Laboratory, Biomedical Research Group in Urology, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain
Rigau M:
Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Spain
Reventós J:
Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Spain
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain
Departament de Ciències Bàsiques, Universitat Internacional de Catalunya, 08017 Barcelona, Spain
Segura MF:
Group of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), 08035 Barcelona, Spain
de Torres I:
Cell Cycle and Cancer Laboratory, Biomedical Research Group in Urology, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain
Department of Pathology, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona (UAB), 08035 Barcelona, Spain
Planas J:
Cell Cycle and Cancer Laboratory, Biomedical Research Group in Urology, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain
Department of Urology, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona (UAB), 08035 Barcelona, Spain
de la Cruz X:
Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain
Group of Clinical and Translational Bioinformatics, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), 08035 Barcelona, Spain
Gomis RR:
Cancer Science Programme, Institute for Research in Biomedicine (IRB-Barcelona), 08028 Barcelona, Spain
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain
Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain
Morote J:
Cell Cycle and Cancer Laboratory, Biomedical Research Group in Urology, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain
Department of Urology, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona (UAB), 08035 Barcelona, Spain
Rodríguez-Barrueco R:
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
Santamaria A:
Cell Cycle and Cancer Laboratory, Biomedical Research Group in Urology, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain
Univ Autonoma Barcelona UAB, Vall dHebron Res Inst VHIR, Grp Clin & Translat Bioinformat, Barcelona 08035, Spain.
Univ Autonoma Barcelona UAB, Vall dHebron Res Inst VHIR, Grp Clin & Translat Bioinformat, Barcelona 08035, Spain
Univ Autonoma Barcelona UAB, Vall dHebron Res Inst VHIR, Grp Clin & Translat Bioinformat, Barcelona 08035, Spain
Green Published, Green Submitted, gold
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