title: The role of glycogen synthase kinase-3β (GSK-3β) in endometrial carcinoma: A carcinogenesis, progression, prognosis, and target therapy marker.
abstract: OBJECTIVE
  Glycogen synthase kinase-3β (GSK-3β) is a serine/threonine kinase involved in cancer development. Herein, we demonstrated the role of GSK-3β in endometrial cancer (EC) and identified new therapeutic targets.
  
  
  RESULTS
  GSK-3β was overexpressed in EC tissues, and was positively correlated with International Federation of Gynecology and Obstetrics (FIGO) staging, dedifferentiation, and myometrial infiltration depth. Besides, GSK-3β overexpression predicted lower cumulative and relapse-free survival rate. si-GSK-3β transfection suppressed cell proliferation, migration, invasion, and promoted cell apoptosis through downregulating NF-kB, Cyclin D1 and MMP9 expression whereas upregulating P21 expression. Bioinformatic predictions and dual-luciferase reporter assays showed that GSK-3β was a possible target of miR-129. MiR-129 transfection reduced GSK-3β expression, and exhibited the same trend as si-GSK-3β transfection in cell function experiments. The nude mouse xenograft assay showed that miR-129 overexpression may suppress tumor growth through downregulating GSK-3β expression. Further studies showed that AZD1080, a GSK-3β inhibitor, could also inhibit EC cell proliferation, migration and invasion, while induced cell apoptosis through modulating relevant genes downstream of GSK-3β signaling.
  
  
  METHODS
  GSK-3β expression was determined in EC tissue and normal endometrial tissues by immunohistochemistry. After GSK-3β down-regulation by si-GSK-3β, microRNA-129 mimic transfection or GSK-3β inhibitor exposure, EC cell phenotypes and related molecules were examined.
  
  
  CONCLUSIONS
  Our results demonstrate for the first time that GSK-3β may be a novel and important therapeutic target for the treatment of endometrial carcinoma. GSK-3β inhibitor AZD1080 may be an effective drug for treating endometrial carcinoma.
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Kai-Xuan
authors.initials: KX
authors.lastname: Sun
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Bo-Liang
authors.initials: BL
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang 100013, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Zong
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D063646:Carcinogenesis; D018269:Carcinoma, Endometrioid / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D011379:Prognosis; D015398:Signal Transduction; D014162:Transfection
chemical_list: D004791:Enzyme Inhibitors; D035683:MicroRNAs; D000071679:Glycogen Synthase Kinase 3 beta
keywords: AZD 1080; GSK-3β; endometrial carcinoma; microRNA-129; tumorigenesis and progression