circPOLR1C Promotes the Development of Esophageal Cancer by Adsorbing miR-361-3p and Regulating Cancer Cell Apoptosis and Metastasis

BACKGROUND: The effect of circular RNA-RNA polymerase I and III subunit C (circPOLR1C) on esophageal cancer (EC) has not been reported. Herein, this study is designed to unveil the effect and the regulatory mechanism of circPOLR1C on EC. METHODS: The expression of circPOLR1C in EC tissues and cells was detected by qRT-PCR. Circular structure, stability, and cell localization of circPOLR1C were confirmed by qRT-PCR, RNase R, actinomycin D, and fluorescence in situ hybridization (FISH) assay. Cell function experiments, nude mouse xenograft, lung transplant model, and HE staining were performed to evaluate the effects of CircPOLR1C on EC in vitro and in vivo. A regulatory relationship between miR-361-3p and circPOLR1C was confirmed by qRT-PCR, circRNA in vivo precipitation, RIP, FISH, CircInteractome database, dual-luciferase reporter assay, and immunohistochemistry. Rescue experiments were applied to assess the effects of miR-361-3p and circPOLR1C on EC cells and tissues. Apoptosis- and epithelial-mesenchymal transformation (EMT)-related gene expressions were quantified by qRT-PCR and Western blot. RESULTS: Highly expressed circPOLR1C in EC was related to tumor differentiation and invasion. circPOLR1C, which mainly exists in the cytoplasm, is a stable circular RNA. circPOLR1C silencing inhibited circPOLR1C expression and EC cell malignant function, while circPOLR1C overexpression promoted the growth of transplanted tumors and lung metastasis. The enrichment of miR-361-3p was higher than that of other targeted miRNAs. circPOLR1C adsorbed miR-361-3p to regulate apoptosis- and EMT-related genes and partially reversed the tumor suppressive effect of miR-361-3p, which was lowly expressed in EC tissues. Silencing the target genes of miR-361-3p also inhibited the malignant development of EC cells. CONCLUSION: circPOLR1C adsorbs miR-361-3p and regulates apoptosis- and EMT-related gene expressions to promote the development of EC.