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

Ivkovic, Tina Catela LU ; Cornella, Helena LU ; Voss, Gjendine LU ; Ku, Anson LU ; Persson, Margareta LU ; Rigo, Robert LU ; Gruvberger-Saal, Sofia K LU ; Saal, Lao H LU orcid and Ceder, Yvonne LU orcid (2023) In Cancers 15(15). p.1-15
Abstract

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™ 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... (More)

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™ 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.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancers
volume
15
issue
15
article number
3892
pages
1 - 15
publisher
MDPI AG
external identifiers
  • scopus:85167731842
  • pmid:37568709
ISSN
2072-6694
DOI
10.3390/cancers15153892
language
English
LU publication?
yes
id
4960f344-c9ac-4c04-a72f-bba850a9128d
date added to LUP
2023-08-21 16:25:24
date last changed
2024-04-20 01:10:13
@article{4960f344-c9ac-4c04-a72f-bba850a9128d,
  abstract     = {{<p>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™ 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.</p>}},
  author       = {{Ivkovic, Tina Catela and Cornella, Helena and Voss, Gjendine and Ku, Anson and Persson, Margareta and Rigo, Robert and Gruvberger-Saal, Sofia K and Saal, Lao H and Ceder, Yvonne}},
  issn         = {{2072-6694}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{15}},
  pages        = {{1--15}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{Functional In Vivo Screening Identifies microRNAs Regulating Metastatic Dissemination of Prostate Cancer Cells to Bone Marrow}},
  url          = {{http://dx.doi.org/10.3390/cancers15153892}},
  doi          = {{10.3390/cancers15153892}},
  volume       = {{15}},
  year         = {{2023}},
}