Circ_DCAF6 potentiates cell stemness and growth in breast cancer through GLI1-Hedgehog pathway

Exp Mol Pathol. 2020 Oct:116:104492. doi: 10.1016/j.yexmp.2020.104492. Epub 2020 Jul 12.

Abstract

Circular RNAs (circRNAs) are extensively revealed as a malignant activator or suppressor in multiple pathological processes including cancer cell stemness and growth. However, the association of circ_DCAF6 with breast cancer (BC) cell growth and stemness has not been well depicted. In this research, qRT-PCR clarified the high level of circ_DCAF6 in BC cells. In functional aspects, BC cells presented suppressed proliferation and stemness in the absence of circ_DCAF6. The potential correlation of circ_DCAF6 with Hedgehog (Hh) pathway was unveiled utilizing its specific inhibitor or agonist in qRT-PCR and functional assays. Circ_DCAF6 positively mediated the expression of GLI1 and its facilitating impacts on BC cell proliferation and stemness required the participation of GLI1-dependent Hh signaling pathway. In depth, circ_DCAF6 post-transcriptionally upregulated GLI1 expression through sequestering miR-616-3p. Rescue experiments verified that the suppressive influence of circ_DCAF6 depletion or miR-616-3p upregulation on BC progression was reversed by GLI1 upregulation. In summary, a probable contribution of circ_DCAF6 to BC cell growth and stemness was elaborated. Circ_DCAF6 assisted in Hh signal pathway activation via the up-regulation of GLI1 by sponging miR-616-3p, generating new thoughts on future direction of antagonizing BC tumorigenesis and stem-like property.

Keywords: BC; GLI1; Stemness; Tumorigenesis; circ_DCAF6; miR-616-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinogenesis / genetics
  • Cell Proliferation / genetics
  • Cell-Free Nucleic Acids / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Hedgehog Proteins / genetics
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Nuclear Proteins / genetics*
  • Signal Transduction / genetics
  • Zinc Finger Protein GLI1 / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell-Free Nucleic Acids
  • DCAF6 protein, human
  • GLI1 protein, human
  • Hedgehog Proteins
  • MIRN616 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • Zinc Finger Protein GLI1