MiR-27a modulates radiosensitivity of triple-negative breast cancer (TNBC) cells by targeting CDC27

Med Sci Monit. 2015 May 6:21:1297-303. doi: 10.12659/MSM.893974.

Abstract

Background: MiR-27a is significantly overexpressed in triple-negative breast cancer (TNBC). However, the exact biological function of MiR-27a in TNBC is not fully understood. In this study, we verified miR-27a expression in TNBC cells and explored how its overexpression modulates radiosensitivity of the cells.

Material/methods: qRT-PCR analysis was performed to study miR-27a expression in TNBC lines MDA-MB-435 and MDA-MB-231 and in normal human breast epithelial cell line MCF10A. Dual luciferase assay was performed to verify a putative downstream target of miR-27a, CDC27. CCK-8 assay was used to assess the influence of miR-27a-CDC27 axis on cell proliferation under irradiation (IR) treatment.

Results: We confirmed significantly higher miR-27a expression in 2 TNBC cell lines--MDA-MB-435 and MDA-MB-231--than in human breast epithelial cell line MCF10A. miR-27a could modulate proliferation and radiosensitivity of TNBC cells. CDC-27 is a direct target of miR-27a and its downregulation conferred increased radioresistance of the cells.

Conclusions: The miR-27a-CDC27 axis might play an important role in modulating response to radiotherapy in TNBC cells. Testing miR-27a expression might be a useful way to identify a subgroup of patients who will benefit from an IR-based therapeutic approach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome / antagonists & inhibitors*
  • Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome / biosynthesis
  • Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome / genetics
  • Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome / physiology
  • Binding Sites
  • Breast / cytology
  • Cell Line, Tumor / radiation effects
  • Cells, Cultured
  • Conserved Sequence
  • Down-Regulation
  • Epithelial Cells / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • HEK293 Cells
  • Humans
  • MicroRNAs / physiology*
  • Molecular Targeted Therapy
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology
  • Oligonucleotides / pharmacology
  • RNA Interference
  • RNA, Small Interfering / pharmacology
  • Radiation Tolerance / genetics
  • Recombinant Fusion Proteins / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology
  • Triple Negative Breast Neoplasms / radiotherapy*
  • Tumor Stem Cell Assay

Substances

  • Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome
  • CDC27 protein, human
  • MIRN27 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • Oligonucleotides
  • RNA, Small Interfering
  • Recombinant Fusion Proteins