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从病毒到癌症:探索丙型肝炎病毒NS3蛋白在致癌过程中的作用

From viruses to cancer: exploring the role of the hepatitis C virus NS3 protein in carcinogenesis.

作者信息

Martineau Carole-Anne, Rivard Nathalie, Bisaillon Martin

机构信息

Département de Biochimie et de Génomique Fonctionnelle, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, 3201 Rue Jean-Mignault, Sherbrooke, QC, J1E 4K8, Canada.

Département d'Immunologie et Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, 3201 Rue Jean-Mignault, Sherbrooke, QC, J1E 4K8, Canada.

出版信息

Infect Agent Cancer. 2024 Aug 27;19(1):40. doi: 10.1186/s13027-024-00606-2.

DOI:10.1186/s13027-024-00606-2
PMID:39192306
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11351854/
Abstract

Hepatitis C virus (HCV) chronically infects approximately 170 million people worldwide and is a known etiological agent of hepatocellular carcinoma (HCC). The molecular mechanisms of HCV-mediated carcinogenesis are not fully understood. This review article focuses on the oncogenic potential of NS3, a viral protein with transformative effects on cells, although the precise mechanisms remain elusive. Unlike the more extensively studied Core and NS5A proteins, NS3's roles in cancer development are less defined but critical. Research indicates that NS3 is implicated in several carcinogenic processes such as proliferative signaling, cell death resistance, genomic instability and mutations, invasion and metastasis, tumor-related inflammation, immune evasion, and replicative immortality. Understanding the direct impact of viral proteins such as NS3 on cellular transformation is crucial for elucidating HCV's role in HCC development. Overall, this review sheds light on the molecular mechanisms used by NS3 to contribute to hepatocarcinogenesis, and highlights its significance in the context of HCV-associated HCC, underscoring the need for further investigation into its specific molecular and cellular actions.

摘要

丙型肝炎病毒(HCV)在全球约1.7亿人中长期感染,是已知的肝细胞癌(HCC)病原体。HCV介导致癌作用的分子机制尚未完全明确。这篇综述文章聚焦于NS3的致癌潜力,NS3是一种对细胞具有转化作用的病毒蛋白,尽管其确切机制仍不清楚。与研究更为广泛的核心蛋白和NS5A蛋白不同,NS3在癌症发展中的作用定义较少但至关重要。研究表明,NS3参与多个致癌过程,如增殖信号传导、细胞死亡抵抗、基因组不稳定和突变、侵袭和转移、肿瘤相关炎症、免疫逃逸以及复制永生。了解诸如NS3等病毒蛋白对细胞转化的直接影响对于阐明HCV在HCC发展中的作用至关重要。总体而言,本综述揭示了NS3促进肝癌发生的分子机制,并强调了其在HCV相关HCC背景下的重要性,突出了进一步研究其具体分子和细胞作用的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b83/11351854/ef820516cd53/13027_2024_606_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b83/11351854/3347b675471e/13027_2024_606_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b83/11351854/91c7044cc15b/13027_2024_606_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b83/11351854/ef820516cd53/13027_2024_606_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b83/11351854/3347b675471e/13027_2024_606_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b83/11351854/91c7044cc15b/13027_2024_606_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b83/11351854/ef820516cd53/13027_2024_606_Fig3_HTML.jpg

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本文引用的文献

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Death by TNF: a road to inflammation.肿瘤坏死因子致死:炎症之路。
Nat Rev Immunol. 2023 May;23(5):289-303. doi: 10.1038/s41577-022-00792-3. Epub 2022 Nov 15.
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The Molecular Interplay between Human Oncoviruses and Telomerase in Cancer Development.人类致癌病毒与端粒酶在癌症发展中的分子相互作用
Cancers (Basel). 2022 Oct 26;14(21):5257. doi: 10.3390/cancers14215257.
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Nonstructural Proteins: The Role in Molecular Mechanisms of Triggering Inflammation.非结构蛋白:在引发炎症分子机制中的作用
Viruses. 2022 Aug 18;14(8):1808. doi: 10.3390/v14081808.
5
Identification and Verification of Ubiquitin D as a Gene Associated with Hepatitis C Virus-Induced Hepatocellular Carcinoma.鉴定和验证泛素 D 作为与丙型肝炎病毒诱导的肝细胞癌相关的基因。
Intervirology. 2022;65(4):195-205. doi: 10.1159/000525543. Epub 2022 Jun 21.
6
Human Pegivirus Type 1: A Common Human Virus That Is Beneficial in Immune-Mediated Disease?人类戊型肝炎病毒 1 型:一种有益免疫介导性疾病的常见人类病毒?
Front Immunol. 2022 May 30;13:887760. doi: 10.3389/fimmu.2022.887760. eCollection 2022.
7
Chemotherapy-induced COX-2 upregulation by cancer cells defines their inflammatory properties and limits the efficacy of chemoimmunotherapy combinations.癌细胞诱导的 COX-2 上调定义了它们的炎症特性,并限制了化疗免疫治疗联合的疗效。
Nat Commun. 2022 Apr 19;13(1):2063. doi: 10.1038/s41467-022-29606-9.
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The HCV Envelope Glycoprotein Down-Modulates NF-κB Signalling and Associates With Stimulation of the Host Endoplasmic Reticulum Stress Pathway.HCV 包膜糖蛋白下调 NF-κB 信号通路并与宿主内质网应激途径的激活相关。
Front Immunol. 2022 Mar 15;13:831695. doi: 10.3389/fimmu.2022.831695. eCollection 2022.
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Br J Cancer. 2022 Jul;127(2):193-201. doi: 10.1038/s41416-022-01775-w. Epub 2022 Mar 15.
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Cancers (Basel). 2022 Jan 22;14(3):552. doi: 10.3390/cancers14030552.