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