Circular RNA hsa_circ_0000073 contributes to osteosarcoma cell proliferation, migration, invasion and methotrexate resistance by sponging miR-145-5p and miR-151-3p and upregulating NRAS

Aging (Albany NY). 2020 Jul 24;12(14):14157-14173. doi: 10.18632/aging.103423. Epub 2020 Jul 24.

Abstract

An increasing number of studies have demonstrated that circular RNAs (circRNAs), as promising therapeutic targets, are essential for diverse human diseases, especially cancer. However, the potential functions and complex mechanisms of most circRNAs in osteosarcoma (OS) are still not fully elucidated. In the present study, we obtained the expression profile of circRNAs from a GEO database (GSE96964) and identified hsa_circ_0000073 as a highly expressed candidate in OS. Overexpression of hsa_circ_0000073 accelerated the proliferation, migration, invasion and MTX resistance of OS cells, and knockdown of hsa_circ_0000073 resulted in the opposite effects. Mechanistically, hsa_circ_0000073 upregulated NRAS expression by targeting miR-145-5p and miR-151-3p in OS cells. In addition, the promotion of OS progression by hsa_circ_000007 was blocked by miR-145-5p and miR-151-3p-mediated NRAS inhibition. In conclusion, hsa_circ_0000073 facilitated the proliferation, migration, invasion and MTX resistance of OS cells through the inhibition of miR-145-5p and miR-151-3p-mediated downregulation of NRAS.

Keywords: NRAS; hsa_circ_0000073; miR-145-5p; miR-151-3p; osteosarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / therapeutic use*
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Drug Resistance, Neoplasm / genetics*
  • GTP Phosphohydrolases / genetics*
  • Humans
  • Membrane Proteins / genetics*
  • Methotrexate / therapeutic use*
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology*
  • RNA, Circular / genetics*

Substances

  • Antimetabolites, Antineoplastic
  • MIRN145 microRNA, human
  • MIRN151a microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • RNA, Circular
  • GTP Phosphohydrolases
  • NRAS protein, human
  • Methotrexate