MicroRNA-520g promotes epithelial ovarian cancer progression and chemoresistance via DAPK2 repression

// Jing Zhang 1, * , Lei Liu 2, * , Yunyan Sun 1 , Jiandong Xiang 1 , Dongmei Zhou 1 , Li Wang 1 , Huali Xu 1 , Xiaoming Yang 1 , Na Du 1 , Meng Zhang 3 , Qin Yan 1 , Xiaowei Xi 1 1 Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People’s Hospital, Shanghai, China 2 Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 3 Department of Pathology, Fudan University Affiliated Shanghai Cancer Center, Shanghai, China * These authors contributed equally to this work Correspondence to: Xiaowei Xi, e-mail: xixiaowei1966@126.com Qin Yan, e-mail: yanqin76@126.com Keywords: miR-520g, epithelial ovarian cancer, progression, chemoresistance, DAPK2 Received: June 17, 2015      Accepted: February 18, 2016      Published: April 01, 2016 ABSTRACT The lack of efficient tumor progression and chemoresistance indicators leads to high mortality in epithelial ovarian cancer (EOC) patients. Dysregulated miR-520g expression is involved in these processes in hepatic and colorectal cancers. In this study, we found that miR-520g expression gradually increased across normal, benign, borderline and EOC tissues. High miR-520g expression promoted tumor progression and chemoresistance to platinum-based chemotherapy, and reduced survival in EOC patients. miR-520g upregulation increased EOC cell proliferation, induced cell cycle transition and promoted cell invasion, while miR-520g downregulation inhibited tumor-related functions. In vivo , overexpression or downregulation of miR-520g respectively generated larger or smaller subcutaneous xenografts in nude mice. Death-associated protein kinase 2 (DAPK2) was a direct target of miR-520g. In 116 EOC tissue samples, miR-520g expression was significantly lower following DAPK2 overexpression. DAPK2 overexpression or miR-520g knockdown reduced EOC cell proliferation, invasion, wound healing and chemoresistance. This study suggests that miR-520g contributes to tumor progression and drug resistance by post-transcriptionally downregulating DAPK2, and that miR-520g may be a valuable therapeutic target in patients with EOC.