miR-513a-5p regulates radiosensitivity of osteosarcoma by targeting human apurinic/apyrimidinic endonuclease
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Nan Dai1, Yi Qing1, Yanping Cun1,2, Zhaoyang Zhong1, Chongyi Li1, Shiheng Zhang1, Jinlu Shan1, Xiao Yang1, Xiaoyan Dai1, Yi Cheng1, He Xiao1, Chengxiong Xu1, Mengxia Li1 and Dong Wang1
1Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, P.R. China
2Department of Neurosurgery, Wuhan General Hospital of Guangzhou Military Command, Wuhan, 430070, P.R. China
Dong Wang, email: [email protected]
Mengxia Li, email: [email protected]
Keywords: miR-513a-5p; osteosarcoma; radioresistance; APE1
Received: January 26, 2016 Accepted: June 01, 2016 Epub: August 02, 2016 Published: May 22, 2018
Radiotherapy in osteosarcoma patients is problematic due to radioresistance; therefore, understanding the mechanism of radioresistance is integral to providing effective radiotherapeutic regimens for osteosarcoma. We now report the activity of an miRNA, miR-513a-5p, in stimulating radiosensitivity of osteosarcoma cells in vitro and in vivo. MiR-513a-5p expression is decreased in osteosarcoma tissue from patients and cultured osteosarcoma cell lines. However, exogenous re-expression of this miRNA in osteosarcoma cell lines, including HOS, U2OS and 9901, can induce sensitization to ionizing radiation. We also confirm that miR-513a-5p suppresses APE1 expression, and that both the redox and DNA repair activity of APE1 were decreased in miR-513a-5p expressing cell lines. By suppressing APE1, miR-513a-5p induces the DNA damage response which stimulates apoptosis after irradiation. Our report establishes miR-513a-5p as a radiosensitizing miRNA and identifies its activity in the suppression of APE1, which could directly lead to radiosensitization.
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