Background

Cervical 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.

Methods

The 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.

Results

CircSOS2 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.

Conclusion

CircSOS2 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.

中文翻译：

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CircSOS2通过靶向miR-543/FNDC3B轴调控增殖、细胞周期、凋亡、迁移、侵袭和糖酵解促进宫颈鳞癌

背景

宫颈鳞状细胞癌 (SCC) 是宫颈癌的常见亚型。环状RNA（circRNA）已被证明是基因调控和恶性肿瘤进展的重要调节因子。因此，研究了环状 RNA 盐过度敏感 2（circSOS2）在 SCC 中的确切作用。

方法

通过实时定量聚合酶链反应 (RT-qPCR) 和蛋白质印迹分析测定 circSOS2、microRNA-543 (miR-543) 和含有 3B 的纤连蛋白 III 型结构域 (FNDC3B) 的相对表达水平。SCC 患者的存活时间百分比与 circSOS2 水平之间的相关性通过 Kaplan-Meier Plotter 分析呈现。通过 MTT 和集落形成试验测量细胞增殖。流式细胞术测定用于评估细胞凋亡和细胞周期分布。通过transwell测定测量迁移和侵袭。通过细胞外酸化率 (ECAR) 测定、葡萄糖测定试剂盒和乳酸测定试剂盒分析糖酵解。通过双荧光素酶报告基因、RNA 免疫沉淀 (RIP) 和 RNA pull-down 试验分析了 miR-543 与 circSOS2 或 FNDC3B 之间的相互作用关系。活体。

结果

CircSOS2在鳞状细胞癌组织和细胞中高表达；此外，其表达水平与预后不良密切相关。功能丧失实验表明，抑制 circSOS2 抑制增殖、细胞周期过程、迁移、侵袭和糖酵解，同时诱导 SCC 细胞凋亡，这被 miR-543 的抑制所推翻。此外，miR-543在鳞状细胞癌组织中下调并与circSOS2表达呈负相关。我们还发现 miR-543 的过表达阻碍了增殖、细胞周期过程、迁移、侵袭和糖酵解，同时通过靶向 FNDC3B 诱导 SCC 细胞凋亡。circSOS2的沉默阻碍了体内肿瘤的发生。

结论

CircSOS2 通过调节 SCC 细胞的增殖、细胞周期、凋亡、迁移、侵袭和糖酵解赋予 SCC 致癌功能，这有助于其与 miR-543 和 FNDC3B 的相互作用。