Circ_0003340 downregulation mitigates esophageal squamous cell carcinoma progression by targeting miR‐940/PRKAA1 axis

AbstractBackgroundEsophageal squamous cell carcinoma (ESCC) is a highly prevalent type of esophageal cancer (EC), usually found at an advanced stage with a high mortality rate, and it is now crucial to find new ways to diagnose and treat ESCC. This study analyzed the function of circular RNA_0003340 (circ_0003340)/microRNA‐940 (miR‐940)/protein kinase AMP‐activated alpha 1 catalytic subunit (PRKAA1) axis in ESCC.MethodsCirc_0003340, miR‐940 and PRKAA1 contents were measured with the application of real‐time quantitative polymerase chain reaction (RT‐qPCR) and western blot. Cell proliferation, cell cycle, apoptosis, migration, invasion and angiogenesis were assessed with a cell counting kit‐8 (CCK8), 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, wound healing, transwell and tube formation assays. We used both the luciferase reporter system and RNA immunoprecipitation (RIP) to analyze the relationship between miR‐940 and circ_0003340 or PRKAA1. Finally, xenograft models were applied to analyze the effect of circ_0003340 on tumor growth in vivo.ResultsUpregulated circ_0003340 and PRKAA1, and downregulated miR‐940 levels were detected in ESCC. Meanwhile, ESCC progression was apparently restrained by circ_0003340 knockdown in vitro. Circ_0003340 acted as a ceRNA for miR‐940 in regulating ESCC progression and miR‐940 was proved to target PRKAA1 to arrest ESCC progression in vitro. Finally, in vivo experiments established that silencing of circ_0003340 slowed tumor growth in vivo.ConclusionCirc_0003340 downregulation mitigated esophageal squamous cell carcinoma progression by targeting miR‐940/PRKAA1 axis.