title: MicroRNA-520g promotes epithelial ovarian cancer progression and chemoresistance via DAPK2 repression.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Huali
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Na
authors.initials: N
authors.lastname: Du
authors.affiliation: Department of Pathology, Fudan University Affiliated Shanghai Cancer Center, Shanghai, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xi
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D064550:Death-Associated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D018450:Disease Progression; D018572:Disease-Free Survival; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D016016:Proportional Hazards Models
chemical_list: C575048:MIRN520 microRNA, human; D035683:MicroRNAs; C579104:DAPK2 protein, human; D064550:Death-Associated Protein Kinases
keywords: DAPK2; chemoresistance; epithelial ovarian cancer; miR-520g; progression