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人乳头瘤病毒驱动的肿瘤发生——远不止E6和E7癌蛋白。

HPV-driven oncogenesis-much more than the E6 and E7 oncoproteins.

作者信息

Janiszewska J, Kostrzewska-Poczekaj M, Wierzbicka M, Brenner J C, Giefing M

机构信息

Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479, Poznan, Poland.

Research & Development Centre, Regional Specialist Hospital Wroclaw, Wroclaw, Poland.

出版信息

J Appl Genet. 2025 Feb;66(1):63-71. doi: 10.1007/s13353-024-00883-y. Epub 2024 Jun 22.

Abstract

High-risk human papillomaviruses are well-established drivers of several cancer types including cervical, head and neck, penile as well as anal cancers. While the E6 and E7 viral oncoproteins have proven to be critical for malignant transformation, evidence is also beginning to emerge suggesting that both host pathways and additional viral genes may also be pivotal for malignant transformation. Here, we focus on the role of host APOBEC genes, which have an important role in molecular editing including in the response to the viral DNA and their role in HPV-driven carcinogenesis. Further, we also discuss data developed suggesting the existence of HPV-derived miRNAs in HPV + tumors and their potential role in regulating the host transcriptome. Collectively, while recent advances in these two areas have added complexity to the working model of papillomavirus-induced oncogenesis, these discoveries have also shed a light onto new areas of research that will be required to fully understand the process.

摘要

高危型人乳头瘤病毒是包括宫颈癌、头颈癌、阴茎癌以及肛门癌在内的多种癌症的公认驱动因素。虽然已证明E6和E7病毒癌蛋白对恶性转化至关重要,但也开始有证据表明宿主通路和其他病毒基因可能对恶性转化也起关键作用。在此,我们重点关注宿主载脂蛋白B mRNA编辑酶催化多肽样(APOBEC)基因的作用,其在分子编辑中具有重要作用,包括对病毒DNA的应答以及在人乳头瘤病毒(HPV)驱动的致癌作用中的作用。此外,我们还讨论了所提出的数据,这些数据表明HPV阳性肿瘤中存在HPV衍生的微小RNA(miRNA)及其在调节宿主转录组中的潜在作用。总的来说,虽然这两个领域的最新进展给乳头瘤病毒诱导肿瘤发生的工作模型增加了复杂性,但这些发现也为全面理解该过程所需的新研究领域带来了启示。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40d6/11761861/b1291d78bd94/13353_2024_883_Fig1_HTML.jpg

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