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CagA蛋白通过/SMAD2/SP1轴调控胃癌的生物学特性

CagA Protein Regulating the Biological Characteristics of Gastric Cancer through the /SMAD2/SP1 axis.

作者信息

Wu Leilei, Jiang Fei, Shen Xiaobing

机构信息

Education Ministry Key Laboratory for Environmental Medicine Engineering, Department of Occupation and Environment Health, School of Public Health, Southeast University, Nanjing 210009, China.

Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing 210009, China.

出版信息

Pathogens. 2022 Jul 28;11(8):846. doi: 10.3390/pathogens11080846.

Abstract

() is a grade Ι carcinogen of gastric cancer (GC), and its high infection rate seriously affects human health. Cytotoxin-associated gene A (CagA) plays a key role in the carcinogenesis of as one of its main virulence factors. is abnormally expressed in patients with GC, associated with the occurrence and development of cancer. However, little is known about the association between CagA and . (1) Background: This study explored the association and mechanism of CagA and in GC. (2) Methods: The sequence was obtained from the NCBI. After sequence optimization, it was connected to the pcDNA3.1 vector to construct a CagA eukaryotic expression plasmid (pcDNA-). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to investigate the expression of and in GC cells. The function of CagA on GC cells was detected by CCK8, wound healing, and Transwell assays. Similarly, the function of was also studied through the above functional experiments after the overexpression and knockdown models had successfully been constructed. The associations among CagA, , and SMAD2/SP1 were evaluated using RNA immunoprecipitation (RIP) and rescue experiments. (3) Results: The expression of was significantly reduced in GC cells, and the expression of was further reduced after CagA induction. Both overexpressed CagA and knockdown cell models enhanced malignant transformation, whereas overexpressed inhibited malignant transformation in vitro. The function of on GC cells could be influenced by CagA. We also found that the influence of on SMAD2 and SP1 could be regulated by CagA. (4) Conclusions: CagA potentially regulates the biological function of GC cells through the /SMAD2/SP1 axis. could be a therapeutic target for GC related to CagA.

摘要

(某物质)是胃癌(GC)的Ⅰ级致癌物,其高感染率严重影响人类健康。细胞毒素相关基因A(CagA)作为其主要毒力因子之一,在(某物质)致癌过程中起关键作用。(某物质)在GC患者中异常表达,与癌症的发生发展相关。然而,关于CagA与(某物质)之间的关联知之甚少。(1)背景:本研究探讨CagA与(某物质)在GC中的关联及机制。(2)方法:从NCBI获取(某物质)序列。序列优化后,连接至pcDNA3.1载体构建CagA真核表达质粒(pcDNA - 某物质)。采用定量实时聚合酶链反应(qRT - PCR)检测GC细胞中(某物质)和(另一物质)的表达。通过CCK8、伤口愈合和Transwell实验检测CagA对GC细胞的作用。同样,在成功构建(某物质)过表达和敲低模型后,也通过上述功能实验研究(某物质)的功能。使用RNA免疫沉淀(RIP)和拯救实验评估CagA、(某物质)和SMAD2/SP1之间的关联。(3)结果:GC细胞中(某物质)表达显著降低,CagA诱导后(另一物质)表达进一步降低。过表达CagA和敲低(某物质)的细胞模型均增强恶性转化,而过表达(某物质)在体外抑制恶性转化。(某物质)对GC细胞的功能可受CagA影响。我们还发现CagA可调节(某物质)对SMAD2和SP1的影响。(4)结论:CagA可能通过(某物质)/SMAD2/SP1轴调节GC细胞的生物学功能。(某物质)可能是与CagA相关的GC的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c2c/9414533/5628f8259c13/pathogens-11-00846-g001.jpg

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