MiR-1301-3p inhibits human breast cancer cell proliferation by regulating cell cycle progression and apoptosis through directly targeting ICT1

Breast Cancer. 2018 Nov;25(6):742-752. doi: 10.1007/s12282-018-0881-5. Epub 2018 Jun 27.

Abstract

Background: MiRNAs regulate a variety of biological processes, such as cell proliferation and apoptosis and play critical roles in cancer progression. Accumulating studies have demonstrated that miR-1301-3p could regulate the development and progression of multiple cancers, but its biological behaviors in breast cancer (BC) are still elusive.

Methods: The expression of miR-1301-3p was determined in BC tissues and cell lines using quantitative real-time PCR analysis. The effects of miR-1301-3p on BC cell growth, proliferation, cell cycle distribution, and apoptosis were also explored in vitro using MTT, colony formation and Flow cytometry assays. The potential target gene of miR-1301-3p was determined by dual-luciferase reporter assay and verified by quantitative real-time PCR and western blot analysis.

Results: We found the expression of miR-1301-3p was observably significantly down-regulated in BC tissues and cell lines. MiR-1301-3p expression in BC tissues was significantly associated with tumor size and clinical stage. Gain-of-function assays demonstrated that miR-1301-3p inhibited the cell growth and proliferation in breast cancer cell lines, MCF-7 and T-47D. Moreover, up-regulation of miR-1301-3p induced cell cycle G0/G1 phase arrest and apoptosis. Mechanistically, up-regulation of miR-1301-3p reduced the expression of CDK4, Cyclin D1, Bcl-2, but elevated the expression of p21, Bad and Bax. ICT1 was confirmed as a direct target of miR-1301-3p. Furthermore, ICT1 overexpression could partially reverse the effects of miR-1301-3p on BC cell proliferation, cell cycle progression and apoptosis.

Conclusion: Our observations suggested that miR-1301-3p inhibits cell proliferation via inducing cell cycle arrest and apoptosis through targeting ICT1, and might be a therapeutic target for BC.

Keywords: Apoptosis; Breast cancer; Cell cycle; Cell proliferation; ICT1; MiR-1301-3p.

MeSH terms

  • Adult
  • Aged
  • Apoptosis*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase 4 / analysis
  • Cyclin-Dependent Kinase 4 / physiology
  • Female
  • G1 Phase Cell Cycle Checkpoints*
  • Humans
  • MicroRNAs / analysis
  • MicroRNAs / physiology*
  • Middle Aged
  • Proteins / genetics*
  • Ribosomal Proteins

Substances

  • MIRN1301 microRNA, human
  • MRPL58 protein, human
  • MicroRNAs
  • Proteins
  • Ribosomal Proteins
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4