CircRNA_103801 accelerates proliferation of osteosarcoma cells by sponging miR-338-3p and regulating HIF-1/Rap1/PI3K-Akt pathway

J Biol Regul Homeost Agents. 2021 May-Jun;35(3):1021-1028. doi: 10.23812/20-725-A.

Abstract

This study aimed to investigate the roles of hsa_circRNA_103801 in the progression of osteosarcoma (OS) cells. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the expression level of circRNA_103801 in OS cells. Cell count kit-8 and Transwell migration and invasion assays were employed to detect the proliferation, migration, and invasion abilities of OS cells. The effects of circRNA_103801 on the apoptosis of OS cells were identified by flow cytometry. The binding relationship between circRNA_103801 and miR-338-3p was verified by bioinformatics analysis. MiR-338-3p level in OS cell lines was detected by RT-qPCR. Additionally, Western blotting was utilized to detect the expression levels of HIF-1, Rap1, PI3K, and Akt in OS cells. The results showed that the expression level of circRNA_103801 was significantly up-regulated in OS patients' tissues. Inhibiting the expression level of circRNA_103801 could attenuate the proliferation, migration, and invasion abilities of OS cells. In addition, the down-regulated expression level of circRNA_103801 could induce cell apoptosis. The results of the luciferase reporter assay suggested that circRNA_103801 could be combined with miR-338-3p, and the RT-qPCR revealed that the miR-338-3p level in OS cells after knockdown of circRNA_103801 was elevated compared with the control group. The results of Western blotting suggested that the expression levels of HIF-1, Rap1, PI3K, and Akt were elevated in OS cells. In conclusion, the circRNA_103801-miR-3388-3p-HIF-1/Rap1/PI3K-Akt pathway could be a therapeutic target of OS.

Keywords: PI3K-Akt; circRNA_103801; miR-3388-3p; osteosarcoma.

MeSH terms

  • Bone Neoplasms* / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • MicroRNAs* / genetics
  • Osteosarcoma* / genetics
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Circular
  • Shelterin Complex
  • Telomere-Binding Proteins
  • Up-Regulation

Substances

  • MIRN338 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Shelterin Complex
  • TERF2IP protein, human
  • Telomere-Binding Proteins
  • Proto-Oncogene Proteins c-akt