Circular RNA circ_0002137 regulated the progression of osteosarcoma through regulating miR-433-3p/ IGF1R axis

J Cell Mol Med. 2022 Mar;26(6):1806-1816. doi: 10.1111/jcmm.16166. Epub 2021 Feb 23.

Abstract

Current clinical treatment targeting osteosarcoma (OS) are limited for OS patients with pulmonary metastasis or relapse, which led to high mortality (70%-85%) for advanced osteosarcoma patients. Although ongoing efforts have been made to illustrate the mechanisms of tumorigenesis and progression in OS; however, it was far for us to learn a comprehensive molecular mechanism implies in OS development. In our study, we implicated a circRNA hsa_circ_0002137, which was higher expressed in osteosarcoma tumours compared with paracancerous tissue. The dysregulated expression pattern was also found in osteosarcoma cell lines. The role of circ_0002137 was explored via down- or up-regulated experiments. It was proved that down-regulation of circ_0002137 suppressed the progress of OS, including cell invasion, cell cycle and cell apoptosis. Furthermore, the correlation between circ_0002137 and miR-433-3p was predicted using bioinformatic tools and verified utilizing RNA pull-down assay and luciferase reporter assay. Interestingly, we found that the inhibitory effect of circ_0002137 on OS was dependent of insulin-like growth factor-1 receptor (IGF1R). In conclusion, it was demonstrated that circ_0002137 could restrain the progression of OS through regulating miR-433-3p/IGF1R axis, providing a comprehensive landscape of circ_0002137 in the generation and development of OS.

Keywords: IGF1R; circRNA; hsa_circ_0002137; miR-433-3p; osteosarcoma.

MeSH terms

  • Bone Neoplasms* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • MicroRNAs* / metabolism
  • Neoplasm Recurrence, Local
  • Osteosarcoma* / metabolism
  • RNA, Circular / genetics
  • Receptor, IGF Type 1 / genetics

Substances

  • IGF1R protein, human
  • MIRN433 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Receptor, IGF Type 1