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

作者：Xueting Hu, Duoguang Wu, Xiaotian He, Huiying Zhao, Zhanghai He, Jiatong Lin, Kefeng Wang, Wenjian Wang, Zihao Pan, Huayue Lin, Minghui Wang · 发表于：Molecular Cancer · 年份：2019 · DOI：10.1186/s12943-019-1095-y · 被引用次数：174 · 研究领域：Circular RNAs in diseases、Connective Tissue Growth Factor Research、GDF15 and Related Biomarkers

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 (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. 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. CONCLUSIONS: CircGSK3β exerts critical roles in promoting ESCC metastasis and ...