title: miR-215 functions as a tumor suppressor in epithelial ovarian cancer through regulation of the X-chromosome-linked inhibitor of apoptosis.
abstract: Epithelial ovarian cancer (EOC) accounts for 90% of all ovarian cancer, which is the third most common gynaecological malignancy worldwide. Dysregulation of miRNAs is involved in the development of different types of EOC. The present study was designed to investigate the role of abnormal expression of miR-215 in the development of EOC and to elucidate the possible molecular mechanisms. mRNA expression of miR-215 was significantly decreased in EOC tissues and cell lines. Upregulation of miR-215 inhibited cell proliferation, promoted apoptosis and increased sensitivity to chemotherapy drugs in EOC cells. In contrast, downregulation of miR-215 increased cell proliferation, inhibited apoptosis and decreased sensitivity to chemotherapy drugs in EOC cells. In addition, the X-chromosome-linked inhibitor of apoptosis (XIAP) expression was significantly increased in EOC tissues and cell lines. Downregulation of XIAP inhibited cell proliferation, promoted apoptosis and increased sensitivity to chemotherapy drugs in EOC cells. Upregulation of miR-215 notably inhibited the expression of XIAP. Moreover, overexpression of XIAP significantly inhibited miR-215-exerted decrease of proliferation, increase of apoptosis and increase of sensitivity to chemotherapy drugs. In conclusion, we identified miR-215 as a potential tumor suppressor in patients with EOC downregulating expression of the oncogenic regulator XIAP. The data demonstrate that miR-215/XIAP pathway may serve as novel therapeutic targets and prognostic markers in patients with EOC.
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yantaxi Road, Xi'an, Shaanxi 710043, P.R. China.
authors.forename: Guanqun
authors.initials: G
authors.lastname: Ge
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yantaxi Road, Xi'an, Shaanxi 710043, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yantaxi Road, Xi'an, Shaanxi 710043, P.R. China.
authors.forename: Ligang
authors.initials: L
authors.lastname: Niu
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yantaxi Road, Xi'an, Shaanxi 710043, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yantaxi Road, Xi'an, Shaanxi 710043, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yantaxi Road, Xi'an, Shaanxi 710043, P.R. China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D015398:Signal Transduction; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C553667:MIRN215 microRNA, human; D035683:MicroRNAs; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D017239:Paclitaxel