Dataset Information
The role of glycogen synthase kinase-3? (GSK-3?) in endometrial carcinoma: A carcinogenesis, progression, prognosis, and target therapy marker.
Ontology highlight
ABSTRACT: Purpose
Glycogen synthase kinase-3? (GSK-3?) is a serine/threonine kinase involved in cancer development. Herein, we demonstrated the role of GSK-3? in endometrial cancer (EC) and identified new therapeutic targets.Results
GSK-3? 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-3? overexpression predicted lower cumulative and relapse-free survival rate. si-GSK-3? 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-3? was a possible target of miR-129. MiR-129 transfection reduced GSK-3? expression, and exhibited the same trend as si-GSK-3? transfection in cell function experiments. The nude mouse xenograft assay showed that miR-129 overexpression may suppress tumor growth through downregulating GSK-3? expression. Further studies showed that AZD1080, a GSK-3? inhibitor, could also inhibit EC cell proliferation, migration and invasion, while induced cell apoptosis through modulating relevant genes downstream of GSK-3? signaling.Experimental design
GSK-3? expression was determined in EC tissue and normal endometrial tissues by immunohistochemistry. After GSK-3? down-regulation by si-GSK-3?, microRNA-129 mimic transfection or GSK-3? inhibitor exposure, EC cell phenotypes and related molecules were examined.Conclusions
Our results demonstrate for the first time that GSK-3? may be a novel and important therapeutic target for the treatment of endometrial carcinoma. GSK-3? inhibitor AZD1080 may be an effective drug for treating endometrial carcinoma.
SUBMITTER: Chen S
PROVIDER: S-EPMC5053670 | biostudies-literature | 2016 May
REPOSITORIES: biostudies-literature
Publications
The role of glycogen synthase kinase-3β (GSK-3β) in endometrial carcinoma: A carcinogenesis, progression, prognosis, and target therapy marker.
Oncotarget 20160501 19
<h4>Purpose</h4>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.<h4>Results</h4>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 ...[more]