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
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Research Support, Non-U.S. Gov't
MeSH terms
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Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome / antagonists & inhibitors*
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Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome / biosynthesis
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Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome / genetics
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Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome / physiology
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Binding Sites
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Breast / cytology
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Cell Line, Tumor / radiation effects
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Cells, Cultured
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Conserved Sequence
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Down-Regulation
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Epithelial Cells / metabolism
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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HEK293 Cells
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Humans
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MicroRNAs / physiology*
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Molecular Targeted Therapy
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Neoplasm Proteins / antagonists & inhibitors*
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology
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Oligonucleotides / pharmacology
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RNA Interference
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RNA, Small Interfering / pharmacology
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Radiation Tolerance / genetics
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Recombinant Fusion Proteins / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Triple Negative Breast Neoplasms / genetics
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Triple Negative Breast Neoplasms / pathology
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Triple Negative Breast Neoplasms / radiotherapy*
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Tumor Stem Cell Assay
Substances
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Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome
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CDC27 protein, human
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MIRN27 microRNA, human
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MicroRNAs
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Neoplasm Proteins
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Oligonucleotides
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RNA, Small Interfering
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Recombinant Fusion Proteins