Circular RNA EPHA3 suppresses progression and metastasis in prostate cancer through the miR-513a-3p/BMP2 axis

J Transl Med. 2023 Apr 28;21(1):288. doi: 10.1186/s12967-023-04132-4.

Abstract

Background: Circular RNAs (circRNAs) may regulate the onset and progression of human malignancies by competitively binding to microRNA (miRNA) sponges, thus regulating the downstream genes. However, aberrant circRNA expression patterns and their biological functions in prostate cancer (PCa) warrant further studies. Our research sought to shed further light on the possible role and molecular mechanism of circEPHA3 action in controlling the growth and metastasis of PCa cells.

Materials and methods: circEPHA3 (has_circ_0066596) was initially screened from a previous circRNA microarray and identified following Actinomycin D and RNase R assays. Fluorescence in situ hybridization, biotin-coupled probe RNA pulldown, and dual-luciferase reporter gene assays were performed to examine the relationship between circEPHA3 and miR-513a-3p. The biological role of circEPHA3 in PCa was assessed by CCK8, wound healing, Transwell assays, and animal experiments.

Results: We identified a novel circular RNA, circEPHA3 (has_circ_0066596), which was down-regulated in high-grade PCa tissues and cell lines. The outcomes of CCK8, wound healing, Transwell assays, and animal experiments revealed that circEPHA3 prohibited the progression and metastasis of PCa in vivo and in vitro. Mechanistically, circEPHA3 was directly bound to miR-513a-3p and regulated the downstream gene, BMP2, thereby serving as a tumor suppressor in PCa.

Conclusions: As a tumor suppressor, circEPHA3 inhibited the proliferation and metastasis of PCa cells through the miR-513a-3p/BMP2 axis, suggesting that circEPHA3 might be a potential therapeutic target for PCa.

Keywords: BMP2; Metastasis; Progression; Prostate cancer; circEPHA3; miR-513a-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Assay
  • Bone Morphogenetic Protein 2 / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • MicroRNAs* / genetics
  • Prostatic Neoplasms* / genetics
  • RNA / genetics
  • RNA, Circular / genetics
  • Receptor, EphA3

Substances

  • RNA, Circular
  • RNA
  • MicroRNAs
  • EPHA3 protein, human
  • Receptor, EphA3
  • BMP2 protein, human
  • Bone Morphogenetic Protein 2