Helicobacter pylori Suppress the Ferroptosis of Gastric Cancer via Inhibiting NAE1-Mediated Neddylation of TFR1.

IF 1.5 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Xinguo Wang, Xingting Ma, Lazati Baheti, Juan Dong, Jie Xu
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引用次数: 0

Abstract

Helicobacter pylori (H. pylori) infection promotes the progression of gastric cancer. The purpose of this study is to investigate the effects of H. pylori infection on gastric cancer and the underlying mechanisms. mRNA levels were determined by reverse transcription quantitative PCR (RT-qPCR). Protein expression was detected by Western blot. Cell viability was detected by Cell Counting Kit-8 assay. Cell proliferation was detected by colony formation assay. Cell mobility was detected by transwell assay. The co-localization of NEDD8 activating enzyme E1 subunit 1 (NAE1) and transferrin receptor 1 (TFR1) was determined by fluorescence in situ hybridization (FISH) assay. TFR1 neddylation was determined using in vitro neddylation assay. H. pylori infection contributed to the proliferation, migration, and invasion of gastric cancer. Moreover, H. pylori infection inhibited erastin-induced ferroptosis of gastric cancer cells. H. pylori infection downregulated NAE1, which promoted the neddylation and protein stability of TFR1. Intriguingly, overexpressed NAE1 inhibited the metastasis as well as promoted the ferroptosis of gastric cancer. H. pylori infection mediates malignant behaviors of gastric cancer via inactivating NAE1/TFR1 signaling. Therefore, targeting NAE1/TFR1 signaling may provide a novel strategy for gastric cancer.

幽门螺杆菌通过抑制nae1介导的TFR1类泛素化抑制胃癌铁下垂。
幽门螺杆菌感染促进胃癌的发展。本研究旨在探讨幽门螺旋杆菌感染对胃癌的影响及其机制。采用反转录定量PCR (RT-qPCR)检测mRNA水平。Western blot检测蛋白表达。细胞计数试剂盒-8法检测细胞活力。用菌落形成法检测细胞增殖情况。transwell法检测细胞迁移率。采用荧光原位杂交(FISH)法测定NEDD8活化酶E1亚基1 (NAE1)和转铁蛋白受体1 (TFR1)的共定位。体外类化法测定TFR1的类化作用。幽门螺旋杆菌感染促进胃癌的增殖、迁移和侵袭。此外,幽门螺杆菌感染可抑制erastin诱导的胃癌细胞铁下垂。幽门螺杆菌感染下调NAE1,促进TFR1的类化修饰和蛋白稳定性。有趣的是,过表达的NAE1抑制了胃癌的转移,促进了胃癌的铁下垂。幽门螺杆菌感染通过使NAE1/TFR1信号失活介导胃癌的恶性行为。因此,靶向NAE1/TFR1信号通路可能为胃癌治疗提供一种新的策略。
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来源期刊
Critical Reviews in Eukaryotic Gene Expression
Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物
CiteScore
2.70
自引率
0.00%
发文量
67
审稿时长
1 months
期刊介绍: Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.
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