title: microRNA-137 promotes apoptosis in ovarian cancer cells via the regulation of XIAP.
abstract: microRNAs (miRNAs) have regulatory roles in various cellular processes, including apoptosis. Recently, X-linked inhibitor of apoptosis protein (XIAP) has been reported to be dysregulated in epithelial ovarian cancer (EOC). However, the mechanism underlying this dysregulation is largely unknown.
  
  
  
  Using bioinformatics and a literature analysis, a panel of miRNAs dysregulated in EOC was chosen for further experimental confirmation from hundreds of miRNAs that were predicted to interact with the XIAP 3'UTR. A dual-luciferase reporter assay was employed to detect the interaction by cellular co-transfection of an miRNA expression vector and a reporter vector with the XIAP 3'UTR fused to a Renilla luciferase reporter. DAPI and TUNEL approaches were used to further determine the effects of an miR-137 mimic and inhibitor on cisplatin-induced apoptosis in ovarian cancer cells.
  
  
  
  We identified eight miRNAs by screening a panel of dysregulated miRNAs that may target the XIAP 3'UTR. The strongest inhibitory miRNA, miR-137, suppressed the activity of a luciferase reporter gene fused with the XIAP 3'UTR and decreased the levels of XIAP protein in SKOV3 ovarian cancer cells. Furthermore, forced expression of miR-137 increased cisplatin-induced apoptosis, and the depressed expression of miR-137 decreased cisplatin-induced apoptosis in SKOV3 and primary EOC cells. Consistently, the disruption of miR-137 via CRISPR/Cas9 inhibited apoptosis and upregulated XIAP in A2780 cells. Furthermore, the effect of miR-137 on apoptosis could be rescued by XIAP in SKOV3 cells. In addition, miR-137 expression is inversely correlated with the level of XIAP protein in both ovarian cancer tissues and cell lines.
  
  
  
  Our data suggest that multiple miRNAs can regulate XIAP via its 3'UTR. miR-137 can sensitise ovarian cancer cells to cisplatin-induced apoptosis, providing new insight into overcoming drug resistance in ovarian cancer.
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Gynecology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Wenshu
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Wan
authors.affiliation: Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Songshan
authors.initials: S
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C545567:MIRN137 microRNA, human; D035683:MicroRNAs; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human