miR-513a-5p regulates radiosensitivity of osteosarcoma by targeting human apurinic/apyrimidinic endonuclease

Abstract

// Nan Dai 1 , Yi Qing 1 , Yanping Cun 1, 2 , Zhaoyang Zhong 1 , Chongyi Li 1 , Shiheng Zhang 1 , Jinlu Shan 1 , Xiao Yang 1 , Xiaoyan Dai 1 , Yi Cheng 1 , He Xiao 1 , Chengxiong Xu 1 , Mengxia Li 1 and Dong Wang 1 1 Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, P.R. China 2 Department of Neurosurgery, Wuhan General Hospital of Guangzhou Military Command, Wuhan, 430070, P.R. China Correspondence to: Dong Wang, email: [e-mail] Mengxia Li, email: [e-mail] Keywords: miR-513a-5p; osteosarcoma; radioresistance; APE1 Received: January 26, 2016      Accepted: June 01, 2016      Epub: August 02, 2016      Published: May 22, 2018 ABSTRACT 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.