Circ_0010220-mediated miR-503-5p/CDCA4 axis contributes to osteosarcoma progression tumorigenesis

Gene. 2020 Dec 30:763:145068. doi: 10.1016/j.gene.2020.145068. Epub 2020 Aug 19.

Abstract

CircRNAs are reported to exert a significant role in modulating genes in cancers, including osteosarcoma progression. Up to now, the function of circ_0010220 in osteosarcoma is still poorly known. The aim of our work was to figure out the potential mechanism of circ_0010220/miR-503-5p/CDCA4 axis in osteosarcoma progression. Firstly, quantitative RT-qPCR was utilized to measure the expression of circ_0010220 in osteosarcoma cells. Then, osteosarcoma cell proliferation, apoptosis, cell cycle, migration and invasion after loss of circ_0010220 were evaluated using CCK-8, flow cytometry, transwell migration, invasion and tumorigenesis experiments respectively. Circ_0010220 expression was markedly increased in osteosarcoma cells. Additionally, knockdown of circ_0010220 significantly depressed tumor growth. CCK-8 analysis indicated that down-regulation of circ_0010220 inhibited osteosarcoma cells proliferation. Flow cytometry assay showed that knockdown of circ_0010220 induced cell apoptosis and blocked cell cycle in the G1 phase. Meanwhile, cell migration an invasion was reduced by circ_0010220. Furthermore, miR-503-5p was predicted as the target for circ_0010220 and miR-503-5p inhibitors reversed cell growth suppressed through silencing circ_0010220. Then, our study demonstrated that Cell Division Cycle-Associated protein 4 (CDCA4) could be a downstream target of miR-503-5p. Additionally, circ_0010220 down-regulation reduced CDCA4 expression level and the inhibitors of miR-503-5p reversed that. In conclusion, we indicated circ_0010220 can be an important biomarker for osteosarcoma via regulating miR-503-5p and CDCA4.

Keywords: CDCA4; Circ_0010220; Osteosarcoma; miR-503-5p.

MeSH terms

  • Animals
  • Apoptosis
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • G1 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism

Substances

  • CDCA4 protein, human
  • Cell Cycle Proteins
  • MIRN503 microRNA, human
  • MicroRNAs
  • RNA, Circular