CircHIPK3 Facilitates the G2/M Transition in Prostate Cancer Cells by Sponging MiR-338-3p

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2020 Jun 18

PMID 32547085

Citations 26

Authors

FengChun Liu

Yanru Fan

Liping Ou

Ting Li

Jiaxin Fan

Limei Duan

Jinxiao Yang

ChunLi Luo

Xiaohou Wu

Affiliations

Soon will be listed here.

Abstract

Background: Circular RNAs (circRNAs) play a crucial role in gene expression regulation. CircHIPK3 is a circRNA derived from Exon 2 of HIPK3 gene and its role in prostate cancer (PCa) is still unclear.

Methods: CCK8 assays, flow cytometry and colony formation assays were performed to assess the effects of circHIPK3 in PCa cells. Bioinformatics analysis, RNA pull-down assay, RNA immunoprecipitation assay (RIP), and luciferase activity assay were performed to dissect the mechanism underlying circHIPK3-mediated G2/M transition in PCa cells.

Results: CircHIPK3 expression was upregulated in PCa cells and prostate cancer tissues. Overexpression of circHIPK3 or circHIPK3 silencing altered PCa viability, proliferation and apoptosis in vitro. CircHIPK3 could sponge miR-338-3p and inhibit its activity, resulting in increased expression of Cdc25B and Cdc2 in vitro.

Conclusion: CircHIPK3 promotes G2/M transition and induces PCa cell proliferation by sponging miR-338-3p and increasing the expression of Cdc25B and Cdc2. CircHIPK3 may play an oncogenic role in PCa.

Citing Articles

The dual role of circHIPK3 in cancer and its implications for multiple drugs resistance: a systematic review and computational approach.

Campelo M, Reis-das-Merces L, Vidal A, da Silva F, de Oliveira A, Monteiro J Front Oncol. 2025; 15:1547889.

PMID: 40061896 PMC: 11885226. DOI: 10.3389/fonc.2025.1547889.

Phytochemical synergies in BK002: advanced molecular docking insights for targeted prostate cancer therapy.

Park M, Choi J, Maharub Hossain Fahim M, Asevedo E, Nurkolis F, Ribeiro R Front Pharmacol. 2025; 16:1504618.

PMID: 40034825 PMC: 11872924. DOI: 10.3389/fphar.2025.1504618.

Multiple roles of circular RNAs in prostate cancer: from the biological basis to potential clinical applications.

Zheng X, Song L, Cao C, Sun S Eur J Med Res. 2025; 30(1):140.

PMID: 40016786 PMC: 11866600. DOI: 10.1186/s40001-025-02382-0.

Circ_0001047 inhibits prostate cancer progression and enhances abiraterone sensitivity via miR-122-5p/FKBP5/PHLPP1/AKT axis in vitro.

Chen Z, Fu S, Shan Y, He Z, Gu J, Wu H Discov Oncol. 2024; 15(1):569.

PMID: 39419900 PMC: 11486870. DOI: 10.1007/s12672-024-01408-z.

Imaging and quantification of human and viral circular RNAs.

Jaijyan D, Yang S, Ramasamy S, Gu A, Zeng M, Subbian S Nucleic Acids Res. 2024; 52(15):e70.

PMID: 39051561 PMC: 11347131. DOI: 10.1093/nar/gkae583.

References

Ngan E, Hashimoto Y, Ma Z, Tsai M, Tsai S . Overexpression of Cdc25B, an androgen receptor coactivator, in prostate cancer. Oncogene. 2003; 22(5):734-9. DOI: 10.1038/sj.onc.1206121. View

Chen L . The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol. 2016; 17(4):205-11. DOI: 10.1038/nrm.2015.32. View

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

Wang Y, Qin H . miR-338-3p targets and suppresses tumorigenicity of prostate cancer cells. Am J Cancer Res. 2019; 8(12):2564-2574. PMC: 6325485. View

Sur S, Agrawal D . Phosphatases and kinases regulating CDC25 activity in the cell cycle: clinical implications of CDC25 overexpression and potential treatment strategies. Mol Cell Biochem. 2016; 416(1-2):33-46. PMC: 4862931. DOI: 10.1007/s11010-016-2693-2. View

Caiment F, Gaj S, Claessen S, Kleinjans J . High-throughput data integration of RNA-miRNA-circRNA reveals novel insights into mechanisms of benzo[a]pyrene-induced carcinogenicity. Nucleic Acids Res. 2015; 43(5):2525-34. PMC: 4357716. DOI: 10.1093/nar/gkv115. View

Kristensen L, Hansen T, Veno M, Kjems J . Circular RNAs in cancer: opportunities and challenges in the field. Oncogene. 2017; 37(5):555-565. PMC: 5799710. DOI: 10.1038/onc.2017.361. View

He S, Zhu L, Liu F, Liu Q, Shao Y, Hua M . Functions of the Vasa gene in Schistosoma japonicum as assessed by RNA interference. Gene. 2017; 638:13-19. DOI: 10.1016/j.gene.2017.09.054. View

Li Y, Zheng F, Xiao X, Xie F, Tao D, Huang C . CircHIPK3 sponges miR-558 to suppress heparanase expression in bladder cancer cells. EMBO Rep. 2017; 18(9):1646-1659. PMC: 5579470. DOI: 10.15252/embr.201643581. View

10.

Chen D, Lu X, Yang F, Xing N . Circular RNA circHIPK3 promotes cell proliferation and invasion of prostate cancer by sponging miR-193a-3p and regulating MCL1 expression. Cancer Manag Res. 2019; 11:1415-1423. PMC: 6388976. DOI: 10.2147/CMAR.S190669. View

11.

Shan K, Liu C, Liu B, Chen X, Dong R, Liu X . Circular Noncoding RNA HIPK3 Mediates Retinal Vascular Dysfunction in Diabetes Mellitus. Circulation. 2017; 136(17):1629-1642. DOI: 10.1161/CIRCULATIONAHA.117.029004. View

12.

Xie W, Regan M, Buyse M, Halabi S, Kantoff P, Sartor O . Metastasis-Free Survival Is a Strong Surrogate of Overall Survival in Localized Prostate Cancer. J Clin Oncol. 2017; 35(27):3097-3104. PMC: 5652387. DOI: 10.1200/JCO.2017.73.9987. View

13.

Sun F, Yu M, Yu J, Liu Z, Zhou X, Liu Y . miR-338-3p functions as a tumor suppressor in gastric cancer by targeting PTP1B. Cell Death Dis. 2018; 9(5):522. PMC: 5943282. DOI: 10.1038/s41419-018-0611-0. View

14.

Zhong Y, Yang J, Xu W, Wang Y, Zheng C, Li B . KCTD12 promotes tumorigenesis by facilitating CDC25B/CDK1/Aurora A-dependent G2/M transition. Oncogene. 2017; 36(44):6177-6189. PMC: 5671937. DOI: 10.1038/onc.2017.287. View

15.

Dudekula D, Panda A, Grammatikakis I, De S, Abdelmohsen K, Gorospe M . CircInteractome: A web tool for exploring circular RNAs and their interacting proteins and microRNAs. RNA Biol. 2015; 13(1):34-42. PMC: 4829301. DOI: 10.1080/15476286.2015.1128065. View

16.

Zeng K, Chen X, Xu M, Liu X, Hu X, Xu T . CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7. Cell Death Dis. 2018; 9(4):417. PMC: 5856798. DOI: 10.1038/s41419-018-0454-8. View

17.

Nie H, Li J, Yang X, Cao Q, Feng M, Xue F . Mineralocorticoid receptor suppresses cancer progression and the Warburg effect by modulating the miR-338-3p-PKLR axis in hepatocellular carcinoma. Hepatology. 2015; 62(4):1145-59. PMC: 4755033. DOI: 10.1002/hep.27940. View

18.

Salzman J, Gawad C, Wang P, Lacayo N, Brown P . Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One. 2012; 7(2):e30733. PMC: 3270023. DOI: 10.1371/journal.pone.0030733. View

19.

Thomas L, Saetrom P . Circular RNAs are depleted of polymorphisms at microRNA binding sites. Bioinformatics. 2014; 30(16):2243-6. PMC: 4207428. DOI: 10.1093/bioinformatics/btu257. View

20.

Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B . Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 2016; 7:11215. PMC: 4823868. DOI: 10.1038/ncomms11215. View