2. Academic Validation
  3. PACT is requisite for prostate cancer cell proliferation

PACT is requisite for prostate cancer cell proliferation

  • Sci Rep. 2025 Oct 21;15(1):36610. doi: 10.1038/s41598-025-20494-9.
Dianne J Beveridge # 1,  Andrew J Woo # 1 2,  Kirsty L Richardson 1,  Rikki A M Brown 1,  Lisa M Stuart 1,  Manjot Singh 1 2,  Andrew D Redfern 1 3 4,  Peter J Leedman 5 6
Affiliations

Affiliations

  • 1 Laboratory for Cancer Medicine, Harry Perkins Institute of Medical Research, and Centre for Medical Research, The University of Western Australia, Crawley, WA, 6009, Australia.
  • 2 Centre for Precision Health, Edith Cowan University, Joondalup, WA, 6027, Australia.
  • 3 School of Medicine and Pharmacology, The University of Western Australia, Crawley, WA, 6009, Australia.
  • 4 Department of Medical Oncology, Fiona Stanley Hospital, Murdoch, WA, 6150, Australia.
  • 5 Laboratory for Cancer Medicine, Harry Perkins Institute of Medical Research, and Centre for Medical Research, The University of Western Australia, Crawley, WA, 6009, Australia. peter.leedman@perkins.org.au.
  • 6 School of Medicine and Pharmacology, The University of Western Australia, Crawley, WA, 6009, Australia. peter.leedman@perkins.org.au.
  • # Contributed equally.
PMID: 41120564 DOI: 10.1038/s41598-025-20494-9
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.

Keywords

Cell-cycle; PACT; PSA; Proliferation; Prostate cancer.

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