CircSOS2 promotes cervical squamous cell carcinoma by regulation of proliferation, cell cycle, apoptosis, migration, invasion, and glycolysis by targeting miR-543/FNDC3B axis

Abstract

BackgroundCervical squamous cell carcinoma (SCC) is a common subtype of cervical cancer. Circular RNAs (circRNAs) have been demonstrated as vital regulators in gene regulation and malignant tumor progression. Therefore, the precise role of circular RNA salt overly-sensitive 2 (circSOS2) was investigated in SCC. MethodsThe relative expression levels of circSOS2, microRNA-543 (miR-543), and Fibronectin type III domain containing 3B (FNDC3B) were determined by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assays. The correlation between percent survival times of SCC patients and circSOS2 level was presented by Kaplan-Meier Plotter analysis. The cell proliferation was measured by MTT and colony-forming assays. Flow cytometry assay was used to assess apoptosis and cell cycle distribution. The migration and invasion were measured by transwell assay. The glycolysis was analyzed by extracellular acidification rate (ECAR) assay, Glucose Assay Kit, and Lactate Assay Kit. The interaction relationship between miR-543 and circSOS2 or FNDC3B was analyzed by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. A xenograft experiment was established to clarify the functional role of circSOS2 inhibition in viv. ResultsCircSOS2 was highly expressed in SCC tissues and cells; besides, its expression level was closely associated with poor prognosis. Loss-of-functional experiments revealed that suppression of circSOS2 repressed proliferation, cell cycle process, migration, invasion, and glycolysis while induced apoptosis in SCC cells, which was overturned by inhibition of miR-543. In addition, miR-543 was downregulated and negatively correlated with circSOS2 expression in SCC tissues. We also found that overexpression of miR-543 impeded proliferation, cell cycle process, migration, invasion, and glycolysis while induced apoptosis in SCC cells by targeting FNDC3B. The silencing of circSOS2 impeded tumorigenesis in vivo. ConclusionCircSOS2 conferred an oncogenic function in SCC by regulation of proliferation, cell cycle, apoptosis, migration, invasion, and glycolysis of SCC cells, which was contributed to its interactions with miR-543 and FNDC3B.