Background: Esophageal 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.
Methods: Circ_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.
Results: Upregulated 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.
Conclusion: Circ_0003340 downregulation mitigated esophageal squamous cell carcinoma progression by targeting miR-940/PRKAA1 axis.
Keywords: ESCC; PRKAA1; circ_0003340; miR-940.
© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.