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Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive malignancies with relatively high morbidity and mortality. Emerging evidence suggests circular RNAs (circRNAs) play critical roles in tumor cell malignancy. However, the biological function and clinical significance of many circRNAs in ESCC remain elusive. Methods: The expression level and clinical implication of circRUNX1 in ESCC tissues were evaluated using qRT-PCR. In vitro and in vivo functional studies were conducted to investigate the underlying biological effects of circRUNX1 on ESCC cell growth and metastasis. Moreover, bioinformatics analysis, RNA sequencing (RNA-seq), RNA immunoprecipitation (RIP) assays, dual-luciferase reporter assays, and rescue experiments were performed to explore the relationships between circRUNX1, miR-449b-5p, Forkhead box protein P3 (FOXP3), and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Results: CircRUNX1 was found to be significantly up-regulated in ESCC tissues and associated with TNM stage and differentiation grade. Functionally, circRUNX1 promoted ESCC cell proliferation and metastasis in vitro and in vivo. CircRUNX1 enhanced FOXP3 expression by competitively sponging miR-449b-5p. Notably, both miR-449b-5p mimics and FOXP3 knockdown restored the effects of circRUNX1 overexpression on cell proliferation and metastasis. Furthermore, IGF2BP2 binding to circRUNX1 prevented its degradation. Conclusions: IGF2BP2 mediated circRUNX1 functions as an oncogenic factor to facilitate ESCC progression through the miR-449b-5p/FOXP3 axis, implying that circRUNX1 has the potential to be a promising diagnostic marker and therapeutic target for ESCC patients. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive gastrointestinal cancers with high incidence and mortality. Therefore, it is necessary to identify novel sensitive and specific biomarkers for ESCC detection and treatment. Circular RNAs (circRNAs) are a type of noncoding RNAs featured by their covalently closed circular structure. This special structure makes circRNAs more stable in mammalian cells, coupled with their great abundance and tissue specificity, suggesting circRNAs may present enormous potential to be explored as valuable prognostic and diagnostic biomarkers for tumor. Mounting studies verified the critical roles of circRNAs in regulating ESCC cells malignant behaviors. Here, we summarized the current progresses in a handful of aberrantly expressed circRNAs, and elucidated their biological function and clinical significance in ESCC, and introduced a series of databases for circRNA research. With the improved advancement in high-throughput sequencing and bioinformatics technique, new frontiers of circRNAs will pave the path for the development of precision treatment in ESCC. [ABSTRACT FROM AUTHOR]