Author Identifier (ORCID)
Andrew J. Woo: https://orcid.org/0000-0003-1198-6373
Manjot Singh: https://orcid.org/0000-0002-0226-083X
Abstract
PACT (encoded by the PRKRA gene) is a double-stranded RNA binding protein with defined antiviral defense and cytoplasmic RNA-induced silencing actions in mammals. We previously described a further role for PACT as a modulator of nuclear receptor (NR)-regulated gene expression. Here, we investigated the role of PACT in prostate cancer (PCa) using a loss-of-function approach. Depletion of PACT in multiple PCa cell lines resulted in a reduction in cell proliferation, but viability was maintained. RNA-sequencing analysis of LNCaP PCa cells ± PACT revealed a depletion of biological processes involved in cell cycle, mitochondrial function, and NR-response pathways in the PACT knockout (KO) cells. In the PACT KO cells, downregulated genes included the androgen-regulated KLK3 (prostate specific antigen, PSA), together with H2AFJ, PSMD5, AQP3, TMEM45B, and SLC22A3, and siRNA-mediated knockdown of these genes reduced cell growth and proliferation in LNCaP cells. Further, reducing PACT or PSA induced cell cycle arrest at G0/G1. Additionally, the hormone-mediated upregulation and AR antagonist-driven downregulation of PSA gene expression were respectively attenuated and enhanced in PACT KO cells. Taken together, these data support a pro-proliferative role for PACT in PCa, and siRNA therapeutic targeting of PACT, or downregulated genes with PACT KO, could represent a new therapeutic approach.
Document Type
Journal Article
Date of Publication
12-1-2025
Volume
15
Issue
1
PubMed ID
41120564
Publication Title
Scientific Reports
Publisher
Nature
School
Centre for Precision Health
RAS ID
84399
Funders
National Health and Medical Research Council
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Beveridge, D. J., Woo, A. J., Richardson, K. L., Brown, R. a. M., Stuart, L. M., Singh, M., Redfern, A. D., & Leedman, P. J. (2025). PACT is requisite for prostate cancer cell proliferation. Scientific Reports, 15. https://doi.org/10.1038/s41598-025-20494-9