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06 May 2015 : Laboratory Research  

MiR-27a Modulates Radiosensitivity of Triple-Negative Breast Cancer (TNBC) Cells by Targeting CDC27

Yong-qiang RenABCDEF, Fengkui FuABCDEF, Jianjun HanABCDEFG

DOI: 10.12659/MSM.893974

Med Sci Monit 2015; 21:1297-1303

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 AND 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.

Keywords: Binding Sites, Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome - physiology, Breast - cytology, Cell Line, Tumor - radiation effects, Conserved Sequence, Epithelial Cells - metabolism, Gene Expression Regulation, Neoplastic - drug effects, HEK293 Cells, MicroRNAs - physiology, Molecular Targeted Therapy, 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 - radiotherapy, Tumor Stem Cell Assay

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750