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circGSK3β promotes metastasis in esophageal squamous cell carcinoma by augmenting β-catenin signaling.
- Source :
-
Molecular cancer [Mol Cancer] 2019 Nov 14; Vol. 18 (1), pp. 160. Date of Electronic Publication: 2019 Nov 14. - Publication Year :
- 2019
-
Abstract
- Background: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn much attention in the pathogenesis of human cancers. However, the role of circRNAs in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we aimed to identify novel circRNAs that regulate ESCC progression and explored their regulatory mechanisms and clinical significance in ESCC.<br />Methods: Differentially expressed circRNAs between ESCC and paired adjacent normal tissues were identified using microarrays. The effects of a specific differentially expressed circRNA (circGSK3β) on tumor progression were explored in vitro and in vivo. Plasma samples from patients with ESCC, benign lesions and healthy controls were subjected to droplet digital PCR (ddPCR) analyses for circGSK3β, and the detection rates of plasma circGSK3β for ESCC were investigated.<br />Results: We demonstrated that upregulated expression of circGSK3β was positively associated with advanced clinical stage and poor outcome in patients with ESCC. We further revealed that circGSK3β promoted ESCC cell migration and invasion via direct interaction with GSK3β and inhibiting GSK3β activity, providing a novel mechanism of circRNA in cancer progression. Importantly, we identified that circGSK3β expression in plasma was a biomarker for detection of ESCC and early stage of ESCC with the area under curve (AUC) of 0.782 and 0.793, respectively.<br />Conclusions: CircGSK3β exerts critical roles in promoting ESCC metastasis and may serve as a novel therapeutic target for ESCC patients. The plasma level of circGSK3β have potential to serve as a novel diagnostic and prognostic biomarker for ESCC detection.
- Subjects :
- Adult
Aged
Biomarkers
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cell Transformation, Neoplastic genetics
Cell Transformation, Neoplastic metabolism
Esophageal Squamous Cell Carcinoma diagnosis
Esophageal Squamous Cell Carcinoma mortality
Female
Fluorescent Antibody Technique
Gene Expression
Gene Expression Regulation, Neoplastic
Glycogen Synthase Kinase 3 beta chemistry
Glycogen Synthase Kinase 3 beta metabolism
Humans
In Situ Hybridization
Male
Middle Aged
Neoplasm Metastasis
Neoplasm Staging
Odds Ratio
Prognosis
Structure-Activity Relationship
beta Catenin chemistry
Esophageal Squamous Cell Carcinoma genetics
Esophageal Squamous Cell Carcinoma metabolism
Glycogen Synthase Kinase 3 beta genetics
RNA, Circular
Signal Transduction
beta Catenin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4598
- Volume :
- 18
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular cancer
- Publication Type :
- Academic Journal
- Accession number :
- 31722716
- Full Text :
- https://doi.org/10.1186/s12943-019-1095-y