Expression of miR-34c induces G2/M cell cycle arrest in breast cancer cells

BMC Cancer. 2014 Jul 26;14:538. doi: 10.1186/1471-2407-14-538.

Abstract

Background: MicroRNA-34 is a family of three miRNAs that have been reported to function as tumor suppressor miRNAs and show decreased expression in various cancers. Here, we examine functions of miR-34c in basal-like breast cancer cells.

Methods: Data from The Cancer Genome Atlas (TCGA) were used for evaluation of expression in primary breast cancers. Cellular processes affected by miR-34c were investigated by thymidine incorporation, Annexin V-assays and cell cycle analysis using breast cancer cell lines. Effects on potential targets were analyzed with qPCR and Western blot.

Results: TCGA data revealed that miR-34c was expressed at lower levels in basal-like breast cancer tumors and low expression was associated with poor prognosis. Ectopic expression of miR-34c in basal-like breast cancer cell lines resulted in suppressed proliferation and increased cell death. Additionally, miR-34c influenced the cell cycle mainly by inducing an arrest in the G2/M phase. We found that expression levels of the known cell cycle-regulating miR-34 targets CCND1, CDK4 and CDK6, were downregulated upon miR-34c expression in breast cancer cell lines. In addition, the levels of CDC23, an important mediator in mitotic progression, were suppressed following miR-34c expression, and siRNAs targeting CDC23 mimicked the effect of miR-34c on G2/M arrest. However, protein levels of PRKCA, a predicted miR-34c target and a known regulator of breast cancer cell proliferation were not influenced by miR-34c.

Conclusions: Together, our results support the role of miR-34c as a tumor suppressor miRNA also in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • G2 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • Neoplasms, Basal Cell / genetics
  • Neoplasms, Basal Cell / pathology*
  • Thymidine / metabolism

Substances

  • Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome
  • CDC23 protein, human
  • MIRN34 microRNA, human
  • MicroRNAs
  • Thymidine