RGD Reference Report - The role of glycogen synthase kinase-3ß (GSK-3ß) in endometrial carcinoma: A carcinogenesis, progression, prognosis, and target therapy marker. - Rat Genome Database

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The role of glycogen synthase kinase-3ß (GSK-3ß) in endometrial carcinoma: A carcinogenesis, progression, prognosis, and target therapy marker.

Authors: Chen, Shuo  Sun, Kai-Xuan  Liu, Bo-Liang  Zong, Zhi-Hong  Zhao, Yang 
Citation: Chen S, etal., Oncotarget. 2016 May 10;7(19):27538-51. doi: 10.18632/oncotarget.8485.
RGD ID: 13524565
Pubmed: PMID:27050373   (View Abstract at PubMed)
PMCID: PMC5053670   (View Article at PubMed Central)
DOI: DOI:10.18632/oncotarget.8485   (Journal Full-text)


PURPOSE: Glycogen synthase kinase-3ß (GSK-3ß) is a serine/threonine kinase involved in cancer development. Herein, we demonstrated the role of GSK-3ß in endometrial cancer (EC) and identified new therapeutic targets.
RESULTS: GSK-3ß 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-3ß overexpression predicted lower cumulative and relapse-free survival rate. si-GSK-3ß 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-3ß was a possible target of miR-129. MiR-129 transfection reduced GSK-3ß expression, and exhibited the same trend as si-GSK-3ß transfection in cell function experiments. The nude mouse xenograft assay showed that miR-129 overexpression may suppress tumor growth through downregulating GSK-3ß expression. Further studies showed that AZD1080, a GSK-3ß inhibitor, could also inhibit EC cell proliferation, migration and invasion, while induced cell apoptosis through modulating relevant genes downstream of GSK-3ß signaling.
EXPERIMENTAL DESIGN: GSK-3ß expression was determined in EC tissue and normal endometrial tissues by immunohistochemistry. After GSK-3ß down-regulation by si-GSK-3ß, microRNA-129 mimic transfection or GSK-3ß inhibitor exposure, EC cell phenotypes and related molecules were examined.
CONCLUSIONS: Our results demonstrate for the first time that GSK-3ß may be a novel and important therapeutic target for the treatment of endometrial carcinoma. GSK-3ß inhibitor AZD1080 may be an effective drug for treating endometrial carcinoma.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
endometrial carcinoma severityIEP 13524565protein:increased expression:endometrium (human)RGD 
endometrial carcinoma severityISOGSK3B (Homo sapiens)13524565; 13524565protein:increased expression:endometrium (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gsk3b  (glycogen synthase kinase 3 beta)

Genes (Mus musculus)
Gsk3b  (glycogen synthase kinase 3 beta)

Genes (Homo sapiens)
GSK3B  (glycogen synthase kinase 3 beta)


Additional Information