Circular RNA circPFKP promotes cell proliferation by activating IMPDH2 in prostate cancer

Cancer Lett. 2022 Jan 1:524:109-120. doi: 10.1016/j.canlet.2021.10.021. Epub 2021 Oct 19.

Abstract

Prostate cancer (PCa), especially castration-resistant PCa, is a common and fatal disease. circRNAs had been confirmed to affect the proliferation of a variety of malignant tumors. Exploring the role of circRNAs in PCa progression and discovering new therapeutic targets are of great importance for the treatment of PCa. In the present study, we found that the expression of circPFKP was significantly increased in PCa tissues compared with adjacent noncancerous prostate tissues, and was correlated with the D'Amico risk classification, N stage, and prognostic stage group of PCa. CircPFKP promotes the proliferation of PCa cells in vitro and in vivo. Suppressing circPFKP induced the G1/S arrest of PCa cells. Mechanistically, circPFKP interacted with IMPDH2, promoted the biogenesis of guanine nucleotides. Moreover, the replenishment of intracellular guanine nucleotides pool reverses the inhibitory effect of knocking-down circPFKP on PCa cell proliferation. hnRNPF might promote circPFKP generation by binding to flanking Alu elements. Our results identify a novel functional interaction of circPFKP with IMPDH2, which promotes the proliferation of PCa cells.

Keywords: Cell cycle; Guanine nucleotide; Inosine monophosphate dehydrogenase 2; Phosphofructokinase; circRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alu Elements / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • IMP Dehydrogenase / genetics*
  • Male
  • Prognosis
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • RNA, Circular / genetics*

Substances

  • RNA, Circular
  • IMP Dehydrogenase
  • IMPDH2 protein, human