Hsa_circ_0002483 inhibited the progression and enhanced the Taxol sensitivity of non-small cell lung cancer by targeting miR-182-5p

Cell Death Dis. 2019 Dec 16;10(12):953. doi: 10.1038/s41419-019-2180-2.

Abstract

In this study, we identified a novel circRNA, circ_0002483, and further investigated its functions in the progression and Taxol resistance of NSCLC. We found that circ_0002483 was expressed at low levels in NSCLC tissues and cell lines. Functional assays indicated that circ_0002483 overexpression significantly inhibited NSCLC cell proliferation and invasion in vitro and in vivo and enhanced the sensitivity of NSCLC cells to Taxol. Mechanistically, circ_0002483 was identified to sponge multiple miRNAs including miR-182-5p (also named miR-182), miR-520q-3p, miR-582-3p, miR-587, and miR-655. In addition, circ_0002483 was also demonstrated to regulate the expression of GRB2, FOXO1, and FOXO3, three target genes of miR-182-5p, by sponging miR-182-5p. Circ_0002483 was demonstrated to inhibit NSCLC progression in vitro and in vivo and enhanced the sensitivity of NSCLC cells to Taxol by sponging miR-182-5p to release the inhibition on GRB2, FOXO1, and FOXO3 mRNAs.

MeSH terms

  • A549 Cells
  • Animals
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Proliferation / drug effects
  • Disease Progression
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Forkhead Box Protein O1 / genetics
  • Forkhead Box Protein O3 / genetics
  • GRB2 Adaptor Protein / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Heterografts
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • RNA, Circular / genetics*

Substances

  • Biomarkers, Tumor
  • FOXO1 protein, human
  • FOXO3 protein, human
  • Forkhead Box Protein O1
  • Forkhead Box Protein O3
  • GRB2 Adaptor Protein
  • GRB2 protein, human
  • MIRN582 microRNA, human
  • MIRN655 microRNA, human
  • MicroRNAs
  • Mirn182 microRNA, human
  • RNA, Circular
  • Paclitaxel