CircDDX17 acts as a competing endogenous RNA for miR-605 in breast cancer progression

Eur Rev Med Pharmacol Sci. 2020 Jun;24(12):6794-6801. doi: 10.26355/eurrev_202006_21668.

Abstract

Objective: Circular RNAs (circRNAs), a novel class of noncoding RNAs, are reported to be involved in the progression of various cancers. CircDDX17 was reported as a tumour suppressor in colorectal cancer. However, the expression and role of circDDX17 in breast cancer remain unclear.

Patients and methods: We used qPCR analysis to reveal the expression levels of circRNAs and miRNAs in breast cancer tissues and cell lines. The target relationship between circRNA and miRNAs was predicted using miRanda and then detected using a Luciferase reporter assay. The effects of circDDX17 and miR-605 on the growth of breast cancer were detected using MTT, colony formation assay and apoptosis analysis.

Results: In this study, low circDDX17 expression was observed in breast cancer tissues and cell lines. Moreover, circDDX17 expression was inversely associated with the clinicopathological parameters of tumour grade and advanced TNM stage (p<0.05). Functionally, overexpressed circDDX17 inhibited cell proliferation and colony formation and promoted cell apoptosis in breast cancer. Mechanistically, circDDX17 directly bound to miR-605, which functions as an oncogene in breast cancer, and its expression was associated with low overall survival of breast cancer patients. Finally, we found that circDDX17 suppressed cell proliferation by regulating cell cycle-related factors (CDK1 and p21), and the effect was reversed by miR-605 mimics.

Conclusions: We identified the downregulation of circDDX17 in breast cancer, and circDDX17 acted as a tumour suppressor by inhibiting proliferation and promoting apoptosis through its function as a sponge of miR-605 in breast cancer, indicating that it serves as a potential biomarker and a therapeutic target for breast cancer.

MeSH terms

  • Apoptosis
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • Cells, Cultured
  • Disease Progression*
  • Female
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*

Substances

  • MIRN605 microRNA, human
  • MicroRNAs
  • RNA, Circular