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31 December 2015 : Laboratory Research  

mir-129-5p Attenuates Irradiation-Induced Autophagy and Decreases Radioresistance of Breast Cancer Cells by Targeting HMGB1

Jing LuoABCDEFG, Jie ChenBCDE, Li HeABCDEFG

DOI: 10.12659/MSM.896661

Med Sci Monit 2015; 21:4122-4129

Abstract

BACKGROUND: This study aimed to determine the role of miR-129-5p in irradiation-induced autophagy in breast cancer cells and to investigate its downstream regulation in autophagy-related radiosensitivity.

MATERIAL AND METHODS: Relative miR-129-5p expression in breast cancer cell lines MCF-7, MDA-MB-231, BT474, and BT549, and in 1 non-tumorigenic breast epithelial cell line, MCF-10A, was compared. The effect of miR-129-5p on irradiation-induced autophagy and radiosensitivity of the cancer cells was explored. The regulative effect of miR-129-5p on HMGB1 and the functional role of this axis in autophagy and radiosensitivity were also studied.

RESULTS: Ectopic expression of miR-129-5p sensitized MDA-MD-231 cells to irradiation, while knockdown of miR-129-5p reduced radiosensitivity of MCF-7 cells. MiR-129-5p overexpression inhibited irradiation-induced autophagy. HMGB1 is a direct functional target of miR-129-5p in breast cancer cells. MiR-129-5p may suppress autophagy and decrease radioresistance of breast cancer cells by targeting HMGB1.

CONCLUSIONS: The miR-129-5p/HMGB1 axis can regulate irradiation-induced autophagy in breast cancer and might be an important pathway in regulating radiosensitivity of breast cancer cells.

Keywords: Autophagy - radiation effects, Apoptosis - radiation effects, Breast Neoplasms - radiotherapy, Cell Proliferation - radiation effects, HMGB1 Protein - metabolism, MCF-7 cells, MicroRNAs - metabolism, Radiation Tolerance

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