Ferroptosis is a specific iron‐dependent cell death form that can induce the production of lipid peroxide, but the roles of circular RNAs (circRNAs) in ferroptosis are completely unaware. Circ‐interleukin‐4 receptor (circIL4R) was reported to express highly in hepatocellular carcinoma (HCC). This study focused on the function of circIL4R dysregulation in tumor progression and ferroptosis of HCC, as well as its molecular mechanism. The quantitative real‐time polymerase chain reaction was implemented for measuring RNA expression. Cell proliferation and survival were evaluated using 3‐(4,5‐dimethylthiazol‐2‐y1)‐2,5‐diphenyl tetrazolium bromide. Apoptotic cells were detected via flow cytometry. The quantification of protein expression was executed through western blotting analysis. The target binding was assessed via the dual‐luciferase reporter, RNA immunoprecipitation, and RNA pull‐down assays. The experiment in vivo was performed using a xenograft model. CircIL4R was abnormally overexpressed in HCC tissues and cells. CircIL4R knockdown impeded oncogenesis and expedited ferroptosis of HCC cells. CircIL4R could directly sponge microRNA‐541‐3p (miR‐541‐3p) and miR‐541‐3p inhibition mitigated the effects of circIL4R knockdown on HCC cells. CircIL4R acted as a miR‐541‐3p sponge to regulate its target glutathione peroxidase 4 (GPX4). GPX4 upregulation relieved the miR‐541‐3p‐induced tumor inhibition and ferroptosis aggravation. CircIL4R played an oncogenic role in HCC via the miR‐541‐3p/GPX4 axis in vivo. Our data suggested that circIL4R served for a tumor promoter and ferroptosis inhibitor in HCC by the miR‐541‐3p/GPX4 network.

中文翻译：

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CircIL4R通过调节miR-541-3p / GPX4轴促进肝细胞癌的发生并抑制肥大症。

Ferroptosis是一种特定的铁依赖性细胞死亡形式，可以诱导脂质过氧化物的产生，但是环状RNA（circRNA）在Ferroptosis中的作用是完全未知的。据报道，Circ-interleukin-4受体（circIL4R）在肝细胞癌（HCC）中高表达。这项研究集中于circIL4R失调在HCC肿瘤进展和肥大症中的作用及其分子机制。实时定量聚合酶链反应用于测量RNA表达。使用3-（4,5-二甲基噻唑-2-y1）-2,5-二苯基溴化四唑评估细胞增殖和存活率。通过流式细胞仪检测凋亡细胞。蛋白质表达的定量通过蛋白质印迹分析进行。通过双荧光素酶报告基因评估靶标结合，RNA免疫沉淀和RNA下拉测定。使用异种移植模型进行体内实验。CircIL4R在HCC组织和细胞中异常过表达。CircIL4R抑制可抑制肝癌的发生并加速HCC细胞的肥大化。CircIL4R可以直接使microRNA‐541‐3p（miR‐541‐3p）和miR‐541‐3p抑制作用减轻circIL4R敲除对HCC细胞的影响。CircIL4R充当miR-541-3p海绵来调节其目标谷胱甘肽过氧化物酶4（GPX4）。GPX4的上调缓解了miR‐541‐3p诱导的肿瘤抑制和肥大症。CircIL4R通过miR-541-3p / GPX4轴在体内在HCC中发挥致癌作用。我们的数据表明circIL4R通过miR-541-3p / GPX4网络在HCC中充当肿瘤启动子和肥大症抑制剂。使用异种移植模型进行体内实验。CircIL4R在HCC组织和细胞中异常过表达。CircIL4R抑制可抑制肝癌的发生并加速HCC细胞的肥大化。CircIL4R可以直接使microRNA‐541‐3p（miR‐541‐3p）和miR‐541‐3p抑制作用减轻circIL4R敲除对HCC细胞的影响。CircIL4R充当miR-541-3p海绵，调节其目标谷胱甘肽过氧化物酶4（GPX4）。GPX4的上调缓解了miR‐541‐3p诱导的肿瘤抑制和肥大症。CircIL4R通过miR-541-3p / GPX4轴在体内在HCC中发挥致癌作用。我们的数据表明circIL4R通过miR-541-3p / GPX4网络在HCC中充当肿瘤启动子和肥大症抑制剂。使用异种移植模型进行体内实验。CircIL4R在HCC组织和细胞中异常过表达。CircIL4R抑制可抑制肝癌的发生并加速HCC细胞的肥大化。CircIL4R可以直接使microRNA‐541‐3p（miR‐541‐3p）和miR‐541‐3p抑制作用减轻circIL4R敲除对HCC细胞的影响。CircIL4R充当miR‐541‐3p海绵，以调节其目标谷胱甘肽过氧化物酶4（GPX4）。GPX4的上调缓解了miR‐541‐3p诱导的肿瘤抑制和肥大症。CircIL4R通过miR-541-3p / GPX4轴在体内在HCC中发挥致癌作用。我们的数据表明circIL4R通过miR-541-3p / GPX4网络在HCC中充当肿瘤启动子和肥大症抑制剂。CircIL4R抑制可抑制肝癌的发生并加速HCC细胞的肥大化。CircIL4R可以直接使microRNA‐541‐3p（miR‐541‐3p）和miR‐541‐3p抑制作用减轻circIL4R敲除对HCC细胞的影响。CircIL4R充当miR-541-3p海绵，调节其目标谷胱甘肽过氧化物酶4（GPX4）。GPX4的上调缓解了miR‐541‐3p诱导的肿瘤抑制和肥大症。CircIL4R通过miR-541-3p / GPX4轴在体内在HCC中发挥致癌作用。我们的数据表明circIL4R通过miR-541-3p / GPX4网络在HCC中充当肿瘤启动子和肥大症抑制剂。CircIL4R抑制可抑制肝癌的发生并加速HCC细胞的肥大化。CircIL4R可以直接使microRNA‐541‐3p（miR‐541‐3p）和miR‐541‐3p抑制作用减轻circIL4R敲除对HCC细胞的影响。CircIL4R充当miR-541-3p海绵，调节其目标谷胱甘肽过氧化物酶4（GPX4）。GPX4的上调缓解了miR‐541‐3p诱导的肿瘤抑制和肥大症。CircIL4R通过miR-541-3p / GPX4轴在体内在HCC中发挥致癌作用。我们的数据表明circIL4R通过miR-541-3p / GPX4网络在HCC中充当肿瘤启动子和肥大症抑制剂。CircIL4R充当miR-541-3p海绵，调节其目标谷胱甘肽过氧化物酶4（GPX4）。GPX4的上调缓解了miR‐541‐3p诱导的肿瘤抑制和肥大症。CircIL4R通过miR-541-3p / GPX4轴在体内在HCC中发挥致癌作用。我们的数据表明circIL4R通过miR-541-3p / GPX4网络在HCC中充当肿瘤启动子和肥大症抑制剂。CircIL4R充当miR-541-3p海绵，调节其目标谷胱甘肽过氧化物酶4（GPX4）。GPX4的上调缓解了miR‐541‐3p诱导的肿瘤抑制和肥大症。CircIL4R通过miR-541-3p / GPX4轴在体内在HCC中发挥致癌作用。我们的数据表明circIL4R通过miR-541-3p / GPX4网络在HCC中充当肿瘤启动子和肥大症抑制剂。