Functional In Vivo Screening Identifies microRNAs Regulating Metastatic Dissemination of Prostate Cancer Cells to Bone Marrow

Catela Ivković, Tina; Cornella, Helena; Voss, Gjendine; Ku, Anson; Persson, Margareta; Rigo, Robert; Gruvberger-Saal, Sofia K.; Saal, Lao H.; Ceder, Yvonne (2023) Functional In Vivo Screening Identifies microRNAs Regulating Metastatic Dissemination of Prostate Cancer Cells to Bone Marrow. Cancers, 15 (15). ISSN 2072-6694

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Abstract

Prostate cancer confined to the prostate is not a cause of death, but when the tumour has metastasized, it is lethal. By using a functional screening method, we identified a microRNA that increased the metastatic spread to bone. We then found that the levels of this microRNA were changed in patients with bone metastases. Our study suggests that this is due to effects on cell growth and colony-formation capacity in the bone microenvironment. Distant metastasis is the major cause of cancer-related deaths in men with prostate cancer (PCa). An in vivo functional screen was used to identify microRNAs (miRNAs) regulating metastatic dissemination of PCa cells. PC3 cells transduced with pooled miRZiP & TRADE; lentivirus library (anti-miRNAs) were injected intraprostatic to 13 NSG mice followed by targeted barcode/anti-miR sequencing. PCa cells in the primary tumours showed a homogenous pattern of anti-miRNAs, but different anti-miRNAs were enriched in liver, lung, and bone marrow, with anti-miR-379 highly enriched in the latter. The bone metastasis-promoting phenotype induced by decreased miR-379 levels was also confirmed in a less metastatic PCa cell line, 22Rv1, where all mice injected intracardially with anti-miR-379-22Rv1 cells developed bone metastases. The levels of miR-379 were found to be lower in bone metastases compared to primary tumours and non-cancerous prostatic tissue in a patient cohort. In vitro functional studies suggested that the mechanism of action was that reduced levels of miR-379 gave an increased colony formation capacity in conditions mimicking the bone microenvironment. In conclusion, our data suggest that specific miRNAs affect the establishment of primary tumours and metastatic dissemination, with a loss of miR-379 promoting metastases in bone.

Item Type:	Article
Uncontrolled Keywords:	prostate cancer; microRNAs; metastases; bone marrow; therapeutics
Subjects:	BIOMEDICINE AND HEALTHCARE > Clinical Medical Sciences
Divisions:	Division of Molecular Medicine
Depositing User:	Josipa Karadžole
Date Deposited:	30 Apr 2026 10:26
URI:	https://fulir.irb.hr:/id/eprint/11849
DOI:	10.3390/cancers15153892

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