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

• Published in: Cancer letters 2022-01, Vol.524, p.109-120
• Main Authors: Wang, Shiyu, Chao, Fan, Zhang, Cong, Han, Dunsheng, Xu, Guoxiong, Chen, Gang
• Format: Article
• Language: English
• Subjects: Alu elements; Alu Elements - genetics; Cancer therapies; Castration; Cell cycle; Cell growth; Cell Line, Tumor; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; circRNA; Circular RNA; Cloning; Disease Progression; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Guanine; Guanine nucleotide; Humans; IMP Dehydrogenase - genetics; Inosine monophosphate dehydrogenase 2; Male; Nucleotides; Phosphofructokinase; Prognosis; Prostate cancer; Prostatic Neoplasms, Castration-Resistant - genetics; Prostatic Neoplasms, Castration-Resistant - pathology; Proteins; Reagents; RNA, Circular - genetics; Therapeutic targets; Tumors
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2021.10.021

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. •Circular RNA-circPFKP is up-regulated in prostate cancer tissues and cells.•circPFKP promotes proliferation of prostate cancer cells in vitro and in vivo.•circPFKP facilitates G1/S transition of cell cycle.•circPFKP activates IMPDH2, promoted the biogenesis of guanine nucleotides.•HNRNPF promote circPFKP generation by binding to its flanking Alu elements.