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环状RNA NGFR的抑制促进胆囊癌细胞的铁死亡。

Inhibition of circRNA NGFR promotes ferroptosis in gallbladder carcinoma cells.

作者信息

Fan Desen, Liu Hui, Hu Bin, Zhou Rongping, Wang Changfeng, Yang Dong

机构信息

Department of Gastroenterology and Pancreatic Surgery, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, Jiangsu, 211100, China.

出版信息

Heliyon. 2024 Apr 25;10(9):e30260. doi: 10.1016/j.heliyon.2024.e30260. eCollection 2024 May 15.

Abstract

BACKGROUND

Gallbladder carcinoma (GBC) is a formidably aggressive malignancy. Circular RNAs (circRNAs) play crucial regulatory roles in cancer. NGFR is a novel circRNA implicated in various types of cancers. The primary goal of this study was to elucidate the role of NGFR in GBC.

METHODS

NGFR variants exhibiting discernible discrepancies were identified using RNA sequencing and validated using real-time PCR. Cell proliferation was assessed using 5-ethynyl-2'-deoxyuridine and Cell Counting Kit-8 assays. The ferroptotic phenotype was characterized by assessing the reactive oxygen species and Fe levels. Western blotting was used to analyze ferroptosis-associated proteins. Superoxide dismutase, malondialdehyde, and glutathione levels were measured using commercially available reagent kits. The severity of mitochondrial damage was evaluated by assessing JC-1, MitoSOX, and ATP activities.

RESULTS

NGFR was upregulated, and its suppression inhibited cell proliferation and increased Fe levels in GBC cells. Furthermore, NGFR downregulation disrupted mitochondrial function.

CONCLUSION

Circular RNA NGFR can impede the advancement of GBC by modulating the ferroptotic phenotype, thereby potentially offering a novel avenue for the clinical diagnosis and treatment strategies of GBC.

摘要

背景

胆囊癌(GBC)是一种极具侵袭性的恶性肿瘤。环状RNA(circRNAs)在癌症中发挥着关键的调节作用。NGFR是一种与多种癌症相关的新型circRNA。本研究的主要目的是阐明NGFR在GBC中的作用。

方法

使用RNA测序鉴定出表现出明显差异的NGFR变体,并通过实时PCR进行验证。使用5-乙炔基-2'-脱氧尿苷和细胞计数试剂盒-8检测评估细胞增殖。通过评估活性氧和铁水平来表征铁死亡表型。使用蛋白质免疫印迹法分析铁死亡相关蛋白。使用市售试剂盒测量超氧化物歧化酶、丙二醛和谷胱甘肽水平。通过评估JC-1、MitoSOX和ATP活性来评估线粒体损伤的严重程度。

结果

NGFR上调,其抑制可抑制GBC细胞的增殖并增加铁水平。此外,NGFR下调会破坏线粒体功能。

结论

环状RNA NGFR可通过调节铁死亡表型来阻碍GBC的进展,从而可能为GBC的临床诊断和治疗策略提供一条新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8009/11076954/7cf1a750a5c4/gr1.jpg

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