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

IF 3.1 2区医学 Q3 IMMUNOLOGY Infectious Agents and Cancer Pub Date : 2024-08-27 DOI:10.1186/s13027-024-00606-2

Carole-Anne Martineau, Nathalie Rivard, Martin Bisaillon

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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.

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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。

全球约有 1.7 亿人长期感染丙型肝炎病毒（HCV），它是肝细胞癌（HCC）的已知病原体。目前还不完全清楚 HCV 介导的致癌分子机制。这篇综述文章的重点是 NS3 的致癌潜力，NS3 是一种对细胞具有转化作用的病毒蛋白，但其确切机制仍难以捉摸。与研究较多的核心蛋白和 NS5A 蛋白不同，NS3 在癌症发展中的作用不太明确，但却至关重要。研究表明，NS3 与多种致癌过程有关，如增殖信号转导、细胞死亡抵抗、基因组不稳定性和突变、侵袭和转移、肿瘤相关炎症、免疫逃避和复制永生。了解 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。总之，本综述揭示了 NS3 促成肝癌发生的分子机制，并强调了其在 HCV 相关 HCC 中的重要性，同时强调了进一步研究其特定分子和细胞作用的必要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Infectious Agents and Cancer ONCOLOGY-IMMUNOLOGY

CiteScore

5.80

自引率

2.70%

发文量

期刊介绍： Infectious Agents and Cancer is an open access, peer-reviewed online journal that encompasses all aspects of basic, clinical, epidemiological and translational research providing an insight into the association between chronic infections and cancer. The journal welcomes submissions in the pathogen-related cancer areas and other related topics, in particular: • HPV and anogenital cancers, as well as head and neck cancers; • EBV and Burkitt lymphoma; • HCV/HBV and hepatocellular carcinoma as well as lymphoproliferative diseases; • HHV8 and Kaposi sarcoma; • HTLV and leukemia; • Cancers in Low- and Middle-income countries. The link between infection and cancer has become well established over the past 50 years, and infection-associated cancer contribute up to 16% of cancers in developed countries and 33% in less developed countries. Preventive vaccines have been developed for only two cancer-causing viruses, highlighting both the opportunity to prevent infection-associated cancers by vaccination and the gaps that remain before vaccines can be developed for other cancer-causing agents. These gaps are due to incomplete understanding of the basic biology, natural history, epidemiology of many of the pathogens that cause cancer, the mechanisms they exploit to cause cancer, and how to interrupt progression to cancer in human populations. Early diagnosis or identification of lesions at high risk of progression represent the current most critical research area of the field supported by recent advances in genomics and proteomics technologies.