CircACAP2 promotes breast cancer proliferation and metastasis by targeting miR-29a/b-3p-COL5A1 axis

Life Sci. 2020 Mar 1:244:117179. doi: 10.1016/j.lfs.2019.117179. Epub 2019 Dec 19.

Abstract

Background: Breast cancer is the most common cancer occurred in female around the world. The occurrence percentage of breast cancer among female who was over 50 years old is >80%. These factors may induce the chance of morbidity, including heavy drinking for a long term, smoking and postmenopausal obesity. Treatment of adjuvant chemotherapeutic and hormonal agents is mostly applied nowadays, which does contribute to the improvement of breast cancer, yet it is still an intractable disease for the side effects it brings. Emerging evidence has proved circular RNAs are involved in gene expression and modulation of biological behaviors. However, the mechanism and functions of circRNA ACAP2 (circACAP2) with respect to breast cancer remain unexplored.

Methods: qRT-PCR analysis was used to detect relevant expression. Bioinformatics analysis was applied to seek miRNAs which might have binding sites with circACAP2 and miR-29a/b-3p. Functional experiments including CCK-8, colony formation assay and flow cytometry assay detected gene function role in breast cancer cells. RIP, RNA pull down and Luciferase reporter assays were carried out to verify binding sites among circACAP2, miR-29a/b-3p and COL5A1.

Results: CircACAP2 expression was prominently elevated in tumorous tissues. Functionally and mechanistically, circACAP2 promoted breast cancer proliferation and motility by sponging miR-29a/b-3p and modulating COL5A1.

Conclusion: Elevated expression of circACAP2 in breast cancer tissues leads to malignant phenotype upon cancerous cells. CircACAP2-miR-29a/b-3p-COL5A1 axis leads to breast cancer tumorigenesis and could hopefully be a novel method for diagnosis and treatment for breast cancer.

Keywords: Breast cancer; COL5A1; circRNA ACAP2; miR-29a-3p; miR-29b-3p.

MeSH terms

  • Adult
  • Apoptosis / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • China
  • Collagen Type V / genetics
  • Collagen Type V / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • RNA, Circular / genetics
  • RNA, Circular / metabolism

Substances

  • ACAP2 protein, human
  • COL5A1 protein, human
  • Collagen Type V
  • MIRN29a microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • RNA, Circular