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MicroRNA-379 Modulates Prostate-Specific Antigen Expression Through Targeting the Androgen Receptor in Prostate Cancer

Cassidy, James R LU ; Persson, Margareta LU ; Voss, Gjendine LU orcid ; Underbjerg, Kira Rosenkilde LU ; Ivkovic, Tina Catela LU ; Bjartell, Anders LU ; Edsjö, Anders LU ; Lilja, Hans LU orcid and Ceder, Yvonne LU orcid (2025) In Cancers 17(19). p.1-13
Abstract


Background: MicroRNA-379 (miR-379) has been reported to play a tumour-suppressing role in several cancer types. Our previous work demonstrated that miR-379 overexpression attenuates the metastatic spread of prostate cancer (PCa) both in vitro and in vivo. However, the underlying mechanisms remain poorly understood.
Methods: To elucidate the mechanisms by which miR-379 affects metastases, we performed a cytokine array to identify secreted proteins modulated by miR-379 dysregulation in a bone microenvironment model. We then assessed the levels of the key candidate, and performed functional studies, including reporter assays, of the transcriptional regulation.
Results: Prostate-specific antigen (PSA)-the clinically widely... (More)


Background: MicroRNA-379 (miR-379) has been reported to play a tumour-suppressing role in several cancer types. Our previous work demonstrated that miR-379 overexpression attenuates the metastatic spread of prostate cancer (PCa) both in vitro and in vivo. However, the underlying mechanisms remain poorly understood.
Methods: To elucidate the mechanisms by which miR-379 affects metastases, we performed a cytokine array to identify secreted proteins modulated by miR-379 dysregulation in a bone microenvironment model. We then assessed the levels of the key candidate, and performed functional studies, including reporter assays, of the transcriptional regulation.
Results: Prostate-specific antigen (PSA)-the clinically widely used blood biomarker for PCa-emerged as the most significantly affected secreted protein. We observed that PSA secretion increased following miR-379 inhibition and decreased with miR-379 overexpression, with parallel changes in intracellular PSA levels. However, our data suggests that miR-379 does not directly regulate PSA expression. Instead, miR-379 appears to downregulate androgen receptor (AR) expression by targeting its 3'-untranslated region (3'-UTR), thereby indirectly reducing PSA transcription through diminished AR-mediated promoter activation. Supporting this indirect mechanism, analysis of clinical samples from prostate cancer patients revealed an inverse correlation between expression of miR-379 in prostatic tissue and serum PSA levels. Furthermore, reduced miR-379 expression was associated with increased levels of AR immunostaining in malignant tissues.
Conclusions: Taken together, these findings suggest that miR-379 negatively regulates PSA secretion indirectly via suppression of AR, and that the interplay between miR-379, AR, and PSA may contribute to the metastatic progression of PCa to bone.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancers
volume
17
issue
19
article number
3245
pages
1 - 13
publisher
MDPI AG
external identifiers
  • scopus:105019217112
  • pmid:41097771
ISSN
2072-6694
DOI
10.3390/cancers17193245
language
English
LU publication?
yes
id
d0d21edd-dd6f-4f3d-b825-00d25abe8a95
date added to LUP
2025-12-02 08:37:50
date last changed
2025-12-17 05:38:29
@article{d0d21edd-dd6f-4f3d-b825-00d25abe8a95,
  abstract     = {{<p><br>
 Background: MicroRNA-379 (miR-379) has been reported to play a tumour-suppressing role in several cancer types. Our previous work demonstrated that miR-379 overexpression attenuates the metastatic spread of prostate cancer (PCa) both in vitro and in vivo. However, the underlying mechanisms remain poorly understood. <br>
 Methods: To elucidate the mechanisms by which miR-379 affects metastases, we performed a cytokine array to identify secreted proteins modulated by miR-379 dysregulation in a bone microenvironment model. We then assessed the levels of the key candidate, and performed functional studies, including reporter assays, of the transcriptional regulation.<br>
 Results: Prostate-specific antigen (PSA)-the clinically widely used blood biomarker for PCa-emerged as the most significantly affected secreted protein. We observed that PSA secretion increased following miR-379 inhibition and decreased with miR-379 overexpression, with parallel changes in intracellular PSA levels. However, our data suggests that miR-379 does not directly regulate PSA expression. Instead, miR-379 appears to downregulate androgen receptor (AR) expression by targeting its 3'-untranslated region (3'-UTR), thereby indirectly reducing PSA transcription through diminished AR-mediated promoter activation. Supporting this indirect mechanism, analysis of clinical samples from prostate cancer patients revealed an inverse correlation between expression of miR-379 in prostatic tissue and serum PSA levels. Furthermore, reduced miR-379 expression was associated with increased levels of AR immunostaining in malignant tissues. <br>
 Conclusions: Taken together, these findings suggest that miR-379 negatively regulates PSA secretion indirectly via suppression of AR, and that the interplay between miR-379, AR, and PSA may contribute to the metastatic progression of PCa to bone.<br>
 </p>}},
  author       = {{Cassidy, James R and Persson, Margareta and Voss, Gjendine and Underbjerg, Kira Rosenkilde and Ivkovic, Tina Catela and Bjartell, Anders and Edsjö, Anders and Lilja, Hans and Ceder, Yvonne}},
  issn         = {{2072-6694}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{19}},
  pages        = {{1--13}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{MicroRNA-379 Modulates Prostate-Specific Antigen Expression Through Targeting the Androgen Receptor in Prostate Cancer}},
  url          = {{http://dx.doi.org/10.3390/cancers17193245}},
  doi          = {{10.3390/cancers17193245}},
  volume       = {{17}},
  year         = {{2025}},
}