Hsa_circ_0063329 inhibits prostate cancer growth and metastasis by modulating the miR-605-5p/tgif2 axis

Cell Cycle. 2023 May;22(9):1101-1115. doi: 10.1080/15384101.2023.2174658. Epub 2023 Feb 5.

Abstract

Circular RNAs play crucial regulatory roles in the progression of various cancers. Nevertheless, the underlying mechanisms of circRNAs in prostate cancer (PCa) proliferation and metastasis remain largely uncertain. Here, we performed circRNA microarray analyses to identify differentially expressed circRNAs in a normal prostate epithelial cell line and PCa cell lines. We found that hsa_circ_0063329 was significantly downregulated in PCa. A series of in vitro and in vivo functional assays showed that overexpression of hsa_circ_0063329 inhibits PCa cell progression, while silencing of hsa_circ_0063329 achieved the opposite effects. Mechanistically, bioinformatics analysis, RNA pulldown, RNA-seq and dual-luciferase reporter assays demonstrated that hsa_circ_0063329 exerts its effect by sponging miR-605-5p to derepress TG-interacting factor 2 (TGIF2) and inactivate the TGF-β pathway. In conclusion, hsa_circ_0063329 inhibits the proliferation and metastasis of PCa via modulation of the miR-605-5p/TGIF2 axis, and targeting hsa_circ_0063329 may provide a promising treatment strategy for aggressive PCa.

Keywords: Prostate cancer; TGIF2; hsa_circ_0063329; miR-605-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Homeodomain Proteins
  • Humans
  • Male
  • MicroRNAs* / genetics
  • Prostatic Neoplasms* / genetics
  • RNA, Circular / genetics
  • Repressor Proteins

Substances

  • MicroRNAs
  • RNA, Circular
  • TGIF2 protein, human
  • Repressor Proteins
  • Homeodomain Proteins
  • MIRN605 microRNA, human

Grants and funding

This work was financed by grants from the National Natural Science Foundation of China [No.82203710], the Science and Technology Plan Project of Guangzhou [No. 202102010150], the Guangdong Basic and Applied Basic Research Foundation [No. 2020A15150100667], the Distinguished Young Talents in Higher Education Foundation of Guangdong Province [No.2019KQNCX115], the China Postdoctoral Science Foundation funded project [No.2019M662865], and the Achievement Cultivation and Clinical Transformation Application Cultivation projects of the First Affiliated Hospital of Guangzhou Medical University [No.ZH201908].