PACT is requisite for prostate cancer cell proliferation

PACT (encoded by the PRKRA gene) is a double-stranded RNA binding protein that has two main functions in mammals: facilitation of antiviral defense mechanisms via the activation of protein kinase RNA (PKR) and retinoic acid-inducible gene 1 (RIG-1), and PACT is also a member of the cytoplasmic RNA-induced silencing complex. We previously described an alternate 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 PCa cell lines resulted in a reduction in cell proliferation; however, they were viable. 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 H2AFJ, PSMD5, AQP3, TMEM45B , SLC22A3, and KLK3 (prostate specific antigen, PSA), and siRNA mediated knockdown of these genes reduced cell growth and proliferation in LNCaP cells. Taken together, these data provide support for PRKRA as a proproliferative gene in PCa and targeting PRKRA , or the genes that are downregulated in PACT KO cells via siRNA therapies, could benefit PCa patient survival.