title: Expression of miR-34c induces G2/M cell cycle arrest in breast cancer cells.
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.
authors: Chandrani
authors: C
authors: Achari
authors: Sofia
authors: S
authors: Winslow
authors: Yvonne
authors: Y
authors: Ceder
authors: Department of Laboratory Medicine, Translational Cancer Research, Lund University, Medicon Village, Building 404:C3, 223 81 Lund, Sweden. Christer.Larsson@med.lu.se.
authors: Christer
authors: C
authors: Larsson
mesh_terms: D064196:Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D018295:Neoplasms, Basal Cell / Q000235:genetics / Q000473:pathology*; D013936:Thymidine / Q000378:metabolism
chemical_list: D064196:Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome; C577440:CDC23 protein, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D013936:Thymidine