高尔基体转运 1B 通过与 TBK1 相互作用激活 NF-κB 信号通路,从而促进宫颈癌的进展。

IF 3.3 3区 医学 Q2 ONCOLOGY Carcinogenesis Pub Date : 2024-08-08 DOI:10.1093/carcin/bgae054
Yixuan Sun, Qihua Peng, Ruiwen Wang, Yifan Yin, Musitaba Mutailifu, Lipeng Hu, Yincheng Teng, Yang Zhou
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引用次数: 0

摘要

作为一种可预防的疾病,宫颈癌(宫颈鳞状细胞癌和宫颈内膜腺癌 - CESC)仍然是全世界发病率和死亡率较高的肿瘤,因此迫切需要有效的治疗策略。这项研究发现高尔基体转运1B(GOLT1B)是宫颈癌发病过程中的一个关键基因。研究人员对基因表达总库(GEO)数据集进行了调查,以确定与正常组织相比,GOLT1B 在宫颈癌组织中的上调情况。此外,通过基因表达谱交互分析(GEPIA)发现,GOLT1B 可预测宫颈癌的不良预后。功能检测表明,GOLT1B 能促进 CESC 在体外和体内的存活和迁移。RNA 测序结果表明,GOLT1B 可能影响了 NF-κB 通路。随后进行的 Western 印迹和双荧光素酶报告实验显示,GOLT1B 与 TBK1 相互作用,调节了 NF-κB 通路。更重要的是,GOLT1B 还能调节免疫细胞的浸润,这表明它在肿瘤微环境中可能发挥作用。总之,GOLT1B 通过与 TBK1 相互作用和增强 NF-κB 信号介导的癌症相关炎症促进了 CESC 的进展,这为我们提供了一种 CESC 靶向治疗的新方法。
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Elevated expression of Golgi Transport 1B promotes the progression of cervical cancer by activating NF-κB signaling pathway via interaction with TBK1.

As a preventable disease, cervical cancer (cervical squamous cell carcinoma and endocervical adenocarcinoma - CESC) remains a tumor with high morbidity and mortality worldwide, underscoring the pressing need for effective treatment strategies. This research identified Golgi transport 1B (GOLT1B) as a critical gene involved in the development of cervical cancer. Gene Expression Omnibus (GEO) datasets were investigated to determine the upregulation of GOLT1B in cervical cancer tissue compared to normal tissue. Besides, GOLT1B was found to predict poor prognosis in cervical cancer by utilizing Gene Expression Profiling Interactive Analysis (GEPIA). The functional assay indicated that GOLT1B promoted CESC viability and migration in vitro and in vivo. RNA sequencing results suggested that GOLT1B likely influenced NF-κB pathway. The subsequent western blot and dual luciferase reporter assay revealed the interaction between GOLT1B and TBK1, modulating the NF-κB pathway. More importantly, GOLT1B was also found to regulate immune cells infiltration, suggesting its potential role in tumor microenvironment. In conclusion, GOLT1B promotes CESC progression via interaction with TBK1 and augmentation of NF-κB signaling-mediated cancer-associated inflammation, which provides us a new approach to CESC target therapy.

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来源期刊
Carcinogenesis
Carcinogenesis 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
95
审稿时长
1 months
期刊介绍: Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).
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