Molecular mechanisms of HPV mediated neoplastic progression.
Molecular mechanisms of HPV mediated neoplastic progression.
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DOI：
10.1186/s13027-016-0107-4
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发表时间：
2016
影响因子：
3.7
通讯作者：
Dwibedi B
中科院分区：
文献类型：
--
作者：
Senapati R;Senapati NN;Dwibedi B
人类乳头瘤病毒是导致子宫颈癌的主要病因，但不是充分的病因。尽管有大量的研究，从低级别鳞状上皮内病变进展到高级别鳞状上皮内病变的潜在机制尚不清楚。病毒基因表达的失调和宿主基因组的不稳定性在病毒介导的致癌作用中起着重要作用。关键事件如病毒整合和表观遗传修饰可能导致病毒和宿主基因表达的失调。本文综述了病毒整合在肿瘤发生中的可能机制和作用。HPV整合开始于由氧化应激或HPV蛋白诱导的DNA损伤或双链断裂，随后的步骤由DNA损伤反应驱动。炎症和氧化应激可能被认为是宫颈癌进展过程中刺激病毒整合和细胞及病毒癌基因失调的辅助因子。所有这些事件以及肿瘤进展中的宿主和病毒遗传和表观遗传修饰也进行了审查，这可能与确定新的预防性治疗策略有关。在缺乏对HPV感染个体的治疗干预的情况下，未来的研究重点应指向预防和逆转HPV整合。DNA损伤反应、敲除整合的HPV序列、siRNA方法、调节携带整合基因组的细胞的选择机制和表观遗传修饰剂是可能的治疗靶点。
Human Papillomavirus is the major etiological agent in the development of cervical cancer but not a sufficient cause. Despite significant research, the underlying mechanisms of progression from a low-grade squamous intraepithelial lesion to high grade squamous intraepithelial lesion are yet to be understood. Deregulation of viral gene expression and host genomic instability play a central role in virus-mediated carcinogenesis. Key events such as viral integration and epigenetic modifications may lead to the deregulation of viral and host gene expression. This review has summarized the available literature to describe the possible mechanism and role of viral integration in mediating carcinogenesis. HPV integration begins with DNA damage or double strand break induced either by oxidative stress or HPV proteins and the subsequent steps are driven by the DNA damage responses. Inflammation and oxidative stress could be considered as cofactors in stimulating viral integration and deregulation of cellular and viral oncogenes during the progression of cervical carcinoma. All these events together with the host and viral genetic and epigenetic modifications in neoplastic progression have also been reviewed which may be relevant in identifying a new preventive therapeutic strategy. In the absence of therapeutic intervention for HPV-infected individuals, future research focus should be directed towards preventing and reversing of HPV integration. DNA damage response, knocking out integrated HPV sequences, siRNA approach, modulating the selection mechanism of cells harboring integrated genomes and epigenetic modifiers are the possible therapeutic targets.
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影响因子：
10.3
作者：
Berumen, J;Ordoñez, RM;Madrigal-de la Campa, A
通讯作者：
Madrigal-de la Campa, A
影响因子：
12.7
作者：
Badaracco, G;Venuti, A;Marcante, ML
通讯作者：
Marcante, ML
影响因子：
3.7
作者：
Barnard, P;Payne, E;McMillan, NAJ
通讯作者：
McMillan, NAJ
影响因子：
3.7
作者：
Cordano, Pablo;Gillan, Victoria;Campo, M. Saveria
通讯作者：
Campo, M. Saveria
影响因子：
3.7
作者：
Brandsma, Janet L.;Sun, Ying;Lizardi, Paul M.;Tuck, David P.;Zelterman, Daniel;Haines, G. Kenneth, III;Martel, Maritza;Harigopal, Malini;Schofield, Kevin;Neapolitano, Matthew
通讯作者：
Neapolitano, Matthew