CircAGFG1 promotes cervical cancer progression via miR-370-3p/RAF1 signaling

BMC Cancer. 2019 Nov 8;19(1):1067. doi: 10.1186/s12885-019-6269-x.

Abstract

Background: In past decades, circular RNAs (circRNAs) have achieved increasing attention because of its regulatory role in different kinds of cancers. However, how circAGFG1 regulates cervical cancer (CC) is still largely undiscovered. This study aims to evaluate the role of a novel circRNAs and related molecular mechanism in CC cells.

Methods: High or low level of circAGFG1 was detected in CC cells or normal cell line with qRT-PCR. The proliferative and migratory abilities of CC cells were assessed with loss-of function assays. The downstream miRNA and mRNA of circAGFG1 were searched out and proved by using bioinformatics analysis and mechanism experiments. Recue assays were designed to confirm the role of circAGFG1/miR-370-3p/RAF1 axis in CC cell activities.

Results: The levels of circAGFG1 was abundant in CC cells in comparison with normal cervical cell End1/E6E7. The inhibitory effect of decreased circAGFG1 level on the proliferative and migratory abilities of CC cells was assessed. CircAGFG1 and miR-370-3p were localized in the cytoplasm and they can interact with each other. Moreover, miR-370-3p was downregulated in CC cells. We also determined the negative effect of miR-370-3p on RAF1. CircAGFG1 could promote RAF1 expression by absorbing miR-370-3p, thereby activating RAF/MEK/ERK pathway. circAGFG1 promoted proliferation and migration of CC cells via enhancing the activity of RAF/MEK/ERK pathway by sponging miR-370-3p and further regulating RAF1.

Conclusion: The results of this study provided new evidence that circAGFG1 acted as a vital regulator in cervical cancer proliferation and migration, giving great promise to apply it as a potential biomarker for diagnosis and therapy in CC treatment.

Keywords: Cervical cancer; RAF1; circAGFG1; miR-370-3p.

MeSH terms

  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • HeLa Cells
  • Humans
  • MicroRNAs / metabolism*
  • Nuclear Pore Complex Proteins / genetics*
  • Nuclear Pore Complex Proteins / metabolism
  • Proto-Oncogene Proteins c-raf / metabolism*
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Signal Transduction / genetics
  • Transfection
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*

Substances

  • AGFG1 protein, human
  • MIRN370 microRNA, human
  • MicroRNAs
  • Nuclear Pore Complex Proteins
  • RNA, Circular
  • RNA-Binding Proteins
  • Proto-Oncogene Proteins c-raf
  • Raf1 protein, human