circGSK3β promotes metastasis in esophageal squamous cell carcinoma by augmenting β-catenin signaling

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. Methods Differentially expressed circRNAs between ESCC and paired adjacent normal tissues were identified using microarrays. The effects of a specific differentially expressed circRNA (circGSK3 beta) 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 circGSK3 beta, and the detection rates of plasma circGSK3 beta for ESCC were investigated. Results We demonstrated that upregulated expression of circGSK3 beta was positively associated with advanced clinical stage and poor outcome in patients with ESCC. We further revealed that circGSK3 beta promoted ESCC cell migration and invasion via direct interaction with GSK3 beta and inhibiting GSK3 beta activity, providing a novel mechanism of circRNA in cancer progression. Importantly, we identified that circGSK3 beta 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. Conclusions CircGSK3 beta exerts critical roles in promoting ESCC metastasis and may serve as a novel therapeutic target for ESCC patients. The plasma level of circGSK3 beta have potential to serve as a novel diagnostic and prognostic biomarker for ESCC detection.