Circ_0000527 promotes osteosarcoma cell progression through modulating miR-646/ARL2 axis

Aging (Albany NY). 2021 Feb 22;13(4):6091-6102. doi: 10.18632/aging.202602. Epub 2021 Feb 22.

Abstract

Accumulating evidence shows that circRNAs play critical roles in the development of human tumors. We observed that circ_0000527 was overexpressed in osteosarcoma cells (SAOS-2, HOS, MG-63 and U2OS) compared in hFOB1.19 cells. We demonstrated that the circ_0000527 level was higher in osteosarcoma specimens than in non-tumor specimens. The ectopic expression of circ_0000527 was shown to induce cell growth, cell cycle progression and the secretion of inflammatory mediators, including IL-1β, IL-6, IL-8 and TNF-α. We demonstrated that circ_0000527 sponges miR-646 in osteosarcoma cells and that ARL2 is a target gene of miR-646. MiR-646 expression was decreased and ARL2 was overexpressed in osteosarcoma cells (SAOS-2, HOS, MG-63 and U2OS) compared to hFOB1.19 cells. Overexpression of circ_0000527 was demonstrated to induce ARL2 expression in MG-63 cells. We showed that miR-646 was downregulated in osteosarcoma specimens compared to that of non-tumor specimens and that the level of circ_0000527 was negatively correlated with miR-646 expression in osteosarcoma specimens. The elevated expression of circ_0000527 was shown to promote cell growth and cell cycle progression by modulating miR-646 expression. The ectopic expression of circ_0000527 was shown to promote cell growth, cell cycle progression and the secretion of inflammatory mediators by modulating ARL2. The present study suggested that the circ_0000527/miR-646/ARL2 axis may be a potential treatment target for osteosarcoma.

Keywords: ARL2; circ_0000527; miR-646; osteosarcoma.

MeSH terms

  • Cell Proliferation / genetics*
  • GTP-Binding Proteins / genetics*
  • Humans
  • MicroRNAs / genetics*
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism*
  • RNA, Circular*

Substances

  • MIRN646 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • ARL2 protein, human
  • GTP-Binding Proteins