Lourenço de Freitas Natália, Deberaldini Maria Gabriela, Gomes Diana, Pavan Aline Renata, Sousa Ângela, Dos Santos Jean Leandro, Soares Christiane P
Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil.
Drugs and Medicines Department, School of Pharmaceutical Science, São Paulo State University (UNESP), Araraquara, Brazil.
Front Cell Dev Biol. 2021 Jan 28;8:592868. doi: 10.3389/fcell.2020.592868. eCollection 2020.
The role of epigenetic modifications on the carcinogenesis process has received a lot of attention in the last years. Among those, histone acetylation is a process regulated by histone deacetylases (HDAC) and histone acetyltransferases (HAT), and it plays an important role in epigenetic regulation, allowing the control of the gene expression. HDAC inhibitors (HDACi) induce cancer cell cycle arrest, differentiation, and cell death and reduce angiogenesis and other cellular events. Human papillomaviruses (HPVs) are small, non-enveloped double-stranded DNA viruses. They are major human carcinogens, being intricately linked to the development of cancer in 4.5% of the patients diagnosed with cancer worldwide. Long-term infection of high-risk (HR) HPV types, mainly HPV16 and HPV18, is one of the major risk factors responsible for promoting cervical cancer development. and assays have demonstrated that HDACi could be a promising therapy to HPV-related cervical cancer. Regardless of some controversial studies, the therapy with HDACi could target several cellular targets which HR-HPV oncoproteins could be able to deregulate. This review article describes the role of HDACi as a possible intervention in cervical cancer treatment induced by HPV, highlighting the main advances reached in the last years and providing insights for further investigations regarding those agents against cervical cancer.
近年来，表观遗传修饰在致癌过程中的作用受到了广泛关注。其中，组蛋白乙酰化是一个由组蛋白去乙酰化酶（HDAC）和组蛋白乙酰转移酶（HAT）调节的过程，它在表观遗传调控中起着重要作用，能够控制基因表达。HDAC抑制剂（HDACi）可诱导癌细胞周期停滞、分化和细胞死亡，并减少血管生成及其他细胞事件。人乳头瘤病毒（HPV）是小型无包膜双链DNA病毒。它们是主要的人类致癌物，在全球4.5%被诊断患有癌症的患者中，与癌症的发生密切相关。高危（HR）HPV类型（主要是HPV16和HPV18）的长期感染是促进宫颈癌发展的主要危险因素之一。 实验和 分析表明，HDACi可能是治疗HPV相关宫颈癌的一种有前景的疗法。尽管存在一些有争议的研究，但HDACi治疗可以靶向多个细胞靶点，而HR-HPV癌蛋白可能会使其失调。这篇综述文章描述了HDACi作为一种可能干预HPV诱导的宫颈癌治疗的作用，强调了近年来取得的主要进展，并为进一步研究这些药物抗宫颈癌提供了见解。
