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

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

⁴

Developmental Tumor Biology Laboratory, Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain

⁵

Cancer Science Programme, Institute for Research in Biomedicine (IRB-Barcelona), 08028 Barcelona, Spain

⁶

Bellvitge Biomedical Research Institute (IDIBELL), 08908 L’Hospitalet de Llobregat, Spain

⁷

Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain

⁸

Departament de Ciències Bàsiques, Universitat Internacional de Catalunya, 08017 Barcelona, Spain

⁹

Group of Translational Research in Child and Adolescent Cancer, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), 08035 Barcelona, Spain

¹⁰

Department of Pathology, University Hospital Vall d’Hebron, Universitat Autònoma de Barcelona (UAB), 08035 Barcelona, Spain

¹¹

Department of Urology, University Hospital Vall d’Hebron, Universitat Autònoma de Barcelona (UAB), 08035 Barcelona, Spain

¹²

Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain

¹³

Group of Clinical and Translational Bioinformatics, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), 08035 Barcelona, Spain

Show full affiliation list

Hide full affiliation list

Authors to whom correspondence should be addressed.

^†

The authors contributed equally to this work.

^‡

The authors contributed equally to this work.

Academic Editor: Lyndsay Rhodes

Cancers 2021, 13(24), 6202; https://doi.org/10.3390/cancers13246202

Received: 21 November 2021 / Revised: 29 November 2021 / Accepted: 3 December 2021 / Published: 9 December 2021

(This article belongs to the Collection The Role of Non-coding RNA in Cancer)

View Full-Text Download PDF

Browse Figures

Review Reports Citation Export

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. View Full-Text

Keywords: miRNA-135b; prostate cancer; bone metastasis; miRNAs

▼ Show Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Supplementary Material

Supplementary File 1:
ZIP-Document (ZIP, 2533 KiB)

Share and Cite

MDPI and ACS Style

Olivan, M.; Garcia, M.; Suárez, L.; Guiu, M.; Gros, L.; Méndez, O.; Rigau, M.; Reventós, J.; Segura, M.F.; de Torres, I.; Planas, J.; de la Cruz, X.; Gomis, R.R.; Morote, J.; Rodríguez-Barrueco, R.; Santamaria, A. Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples. Cancers 2021, 13, 6202. https://doi.org/10.3390/cancers13246202

AMA Style

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. Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples. Cancers. 2021; 13(24):6202. https://doi.org/10.3390/cancers13246202

Chicago/Turabian Style

Olivan, Mireia, 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, and Anna Santamaria. 2021. "Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples" Cancers 13, no. 24: 6202. https://doi.org/10.3390/cancers13246202

Find Other Styles

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Abstract views Pdf views Html views

Article Menu

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

Simple Summary

Abstract

Supplementary Material

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI