Circ_ZFR affects FABP7 expression to regulate breast cancer progression by acting as a sponge for miR-223-3p

Thorac Cancer. 2022 May;13(9):1369-1380. doi: 10.1111/1759-7714.14401. Epub 2022 Mar 30.

Abstract

Background: Breast cancer (BC) is a common malignancy in women. Circular RNAs (circRNAs) have been reported to play a key role in the development of BC; however, the effect of circular RNA zinc finger RNA binding protein (circ_ZFR) in BC is unknown.

Methods: Abundances of circ_ZFR, fatty acid binding protein 7 (FABP7), and microRNA-223-3p (miR-223-3p) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The circular structure of circ_ZFR was validated by RNase R treatment. Cell proliferation, migration, invasion, and apoptosis were assessed by colony formation, cell counting kit-8, Transwell, flow cytometry assays, respectively. All protein levels were determined by Western blot. Dual-luciferase reporter assay was used to confirm the relationship between miR-223-3p and circ_ZFR or FABP7. A xenograft model was established to understand the effect of circ_ZFR on BC cell growth in vivo.

Results: The expression levels of circ_ZFR and FABP7 were higher in BC tissues and cell lines, whereas miR-223-3p expression was lower. Knockdown of circ_ZFR or FABP7 in BC cells reduced proliferation, migration, invasion, and epithelial mesenchymal transition (EMT), and induced apoptosis in vitro, whereas the opposite effects were observed in circ_ZFR-overexpressed cells. Furthermore, circ_ZFR might act as a sponge for miR-223-3p to regulate FABP7 expression, thereby promoting the progression of BC cells in vitro and in vivo.

Conclusion: Circ_ZFR might act as a miRNA sponge for miR-223-3p to regulate FABP7, thereby promoting proliferation, migration, invasion, and EMT of BC cells, and inhibiting cell apoptosis.

Keywords: Circ_ZFR; FABP7; breast cancer; miR-223-3p.

MeSH terms

  • Breast Neoplasms* / pathology
  • Cell Proliferation / genetics
  • Fatty Acid-Binding Protein 7
  • Female
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • FABP7 protein, human
  • Fatty Acid-Binding Protein 7
  • MIRN223 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Tumor Suppressor Proteins