CircAGFG1 sponges miR-203 to promote EMT and metastasis of non-small-cell lung cancer by upregulating ZNF281 expression

Thorac Cancer. 2019 Aug;10(8):1692-1701. doi: 10.1111/1759-7714.13131. Epub 2019 Jun 27.

Abstract

The circRNA circAGFG1 is reported to be important in triple-negative breast cancer progression. However, the mechanism of circAGFG1 in non-small-cell lung cancer (NSCLC) remains unknown. In this study, expression of circAGFG1 was determined by real-time PCR in 20 pairs of NSCLC tissues and adjacent tissues. Next, functional experiments with circAGFG1 were performed in vitro to evaluate the role of circAGFG1 in tumor metastasis and growth. Meanwhile, a dual luciferase reporter assay, RNA pull-down and RNA immunoprecipitation experiments were used to explore the interaction between circAGFG1 and miR-203. Our results revealed that expression levels of circAGFG1 and miR-203 are upregulated in non-small-cell lung cancer tissues. CircAGFG1 enhances NSCLC cell proliferation, invasion, migration and epithelial-mesenchymal transition in vitro. Mechanistic analyses indicated that circAGFG1 acts as a sponge for miR-203 to repress the effect of miR-203 on its target, ZNF281. In conclusion, our study suggests that circAGFG1 promotes NSCLC growth and metastasis though a circAGFG1/miR-203/ZNF281 axis and may represent a novel therapeutic target.

Keywords: ZNF281; circAGFG1; miR-203; non-small-cell lung cancer.

MeSH terms

  • A549 Cells
  • Binding Sites
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis
  • Nuclear Pore Complex Proteins / biosynthesis
  • Nuclear Pore Complex Proteins / genetics
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / genetics
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transfection
  • Up-Regulation

Substances

  • AGFG1 protein, human
  • MIRN203 microRNA, human
  • MicroRNAs
  • Nuclear Pore Complex Proteins
  • RNA-Binding Proteins
  • Repressor Proteins
  • ZNF281 protein, human