Currently, multiple circular RNAs (circRNAs) have been verified to act as essential regulators in the progression of gastric cancer (GC). We aimed to investigate the role of circ_0008035 in GC progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to measure the expression of circ_0008035 and miR-599. 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was employed to evaluate cell proliferation and ferroptosis. Western blot assay was performed to measure the levels of cyclin D1, proliferating cell nuclear antigen (PCNA) and eukaryotic initiation factor 4A1 (EIF4A1). Flow cytometry analysis was conducted to assess cell apoptosis. The iron accumulation, lipid peroxidation and mitochondrial membrane potential were examined by relevant kits. Dual-luciferase reporter assay was conducted to determine the targeting relationship between miR-599 and circ_0008035 or EIF4A1. A murine xenograft model was established to investigate the function of circ_0008035 in vivo. Circ_0008035 was up-regulated in GC tissues and cells. Silencing of circ_0008035 repressed cell proliferation and induced cell apoptosis and ferroptosis in GC cells. Circ_0008035 acted as a sponge of miR-599. The effects of circ_0008035 knockdown on GC cell proliferation, apoptosis and ferroptosis were abolished by miR-599 inhibition. EIF4A1 was confirmed to be a target gene of miR-599. Circ_0008035 knockdown inhibited EIF4A1 expression by targeting miR-599. Moreover, the suppressive role of circ_0008035 deficiency in GC progression could be restored by EIF4A1. Additionally, circ-0008035 knockdown hampered tumorigenesis in vivo. Circ_0008035 promoted GC cell growth and repressed apoptosis and ferroptosis by up-regulating EIF4A1 through sponging miR-599.

中文翻译：

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Circ_0008035通过miR-599/EIF4A1轴促进胃癌细胞增殖并抑制细胞凋亡和铁死亡

目前，多个环状 RNA（circRNA）已被证实在胃癌（GC）的进展中充当重要的调节因子。我们旨在研究 circ_0008035 在 GC 进程中的作用。定量实时聚合酶链反应 (qRT-PCR) 用于测量 circ_0008035 和 miR-599 的表达。3-(4,5-二甲基-2-噻唑基)-2, 5-二苯基-2-H-溴化四唑 (MTT) 测定用于评估细胞增殖和铁死亡。进行蛋白质印迹测定以测量细胞周期蛋白 D1、增殖细胞核抗原 (PCNA) 和真核起始因子 4A1 (EIF4A1) 的水平。进行流式细胞术分析以评估细胞凋亡。通过相关试剂盒检测铁积累、脂质过氧化和线粒体膜电位。进行双荧光素酶报告基因检测以确定 miR-599 与 circ_0008035 或 EIF4A1 之间的靶向关系。建立小鼠异种移植模型以研究 circ_0008035 在体内 的功能。Circ_0008035 在 GC 组织和细胞中上调。circ_0008035的沉默抑制GC细胞的细胞增殖并诱导细胞凋亡和铁死亡。Circ_0008035 充当 miR-599 的海绵。miR-599 抑制消除了 circ_0008035 敲低对 GC 细胞增殖、细胞凋亡和铁死亡的影响。EIF4A1 被证实是 miR-599 的靶基因。Circ_0008035 敲低通过靶向 miR-599 抑制 EIF4A1 表达。此外，EIF4A1 可以恢复 circ_0008035 缺陷在 GC 进展中的抑制作用。此外，circ-0008035 敲低阻碍了体内肿瘤发生。