Circ_0023984 Facilitates Esophageal Squamous Cell Carcinoma Progression by Regulating miR-433-3p/REV3L Axis.

backgroundIt has been revealed that circular RNAs (circRNAs) play an important role in regulating the malignant phenotype of tumor cells, thus involving in the progression of malignancies. However, the role of circ_0023984 in esophageal squamous cell carcinoma (ESCC) remains largely unclear.

methodsThe quantitative real-time polymerase chain reaction and Western blot assays were used to detect the expression of circ_0023984, microRNA (miR)-443-3p, and protein reversionless 3-like (REV3L). In vitro and in vivo assays were performed using cell counting kit-8, colony formation, transwell, wound healing, flow cytometry, and xenograft assays. The interaction miR-433-3p and circ_0023984 or REV3L was confirmed by dual-luciferase reporter, pull-down or RIP assays.

resultsCirc_0023984 was highly expressed in ESCC tissues and cells, knockdown of circ_0023984 suppressed cancer cell proliferation, migration, invasion, and promoted cell apoptosis in vitro. Mechanistic analysis confirmed that circ_0023984 functioned as a sponge for miR-433-3p to positively regulate the expression of REV3L that was verified to be a target of miR-433-3p. Circ_0023984 knockdown repressed the tumorigenesis of ESCC cells via targeting miR-433-3p. Additionally, miR-433-3p performed anti-proliferative, anti-migratory, and anti-invasive abilities in ESCC cells, which were reversed by REV3L overexpression. Pre-clinically, silencing of circ_0023984 suppresses the tumorigenesis and growth of xenografts in nude mice.

conclusionCirc_0023984 exerted an oncogenic role in ESCC tumorigenesis and aggressiveness through promoting cell growth, migration, and invasion via miR-433-3p/REV3L axis.