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褪黑素在表观基因组学时代作为口腔癌辅助治疗手段的潜力

Potential of Melatonin as Adjuvant Therapy of Oral Cancer in the Era of Epigenomics.

作者信息

Capote-Moreno Ana, Ramos Eva, Egea Javier, López-Muñoz Francisco, Gil-Martín Emilio, Romero Alejandro

机构信息

Department of Oral and Maxillofacial Surgery, University Hospital La Princesa, Autonomous University of Madrid,, 28006 Madrid, Spain.

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040 Madrid, Spain.

出版信息

Cancers (Basel). 2019 Nov 2;11(11):1712. doi: 10.3390/cancers11111712.

DOI:10.3390/cancers11111712
PMID:31684096
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6895876/
Abstract

The wide variety of epigenetic controls available is rapidly expanding the knowledge of molecular biology even overflowing it. At the same time, it can illuminate unsuspected ways of understanding the etiology of cancer. New emerging therapeutic horizons, then, promise to overcome the current antitumor strategies need. The translational utility of this complexity is particularly welcome in oral cancer (OC), in which natural history is alarmingly disappointing due to the invasive and mutilating surgery, the high relapsing rate, the poor quality of life and the reduced survival after diagnosis. Melatonin activates protective receptor-dependent and receptor-independent processes that prevent tissue cancerisation and inhibit progressive tumor malignancy and metastasis. Related evidence has shown that melatonin pleiotropy encompasses gene expression regulation through all the three best-characterized epigenetic mechanisms: DNA methylation, chromatin modification, and non-coding RNA. OC has received less attention than other cancers despite prognosis is usually negative and there are no significant therapy improvements recorded in the past decade. However, a large research effort is being carried out to elucidate how melatonin´s machinery can prevent epigenetic insults that lead to cancer. In the light of recent findings, a comprehensive examination of biochemistry through which melatonin may reverse epigenetic aberrations in OC is an extraordinary opportunity to take a step forward in the clinical management of patients.

摘要

现有的各种各样的表观遗传调控手段正在迅速拓展分子生物学知识,甚至使其趋于饱和。与此同时,它能够揭示一些意想不到的理解癌症病因的途径。于是,新出现的治疗前景有望克服当前抗肿瘤策略的需求。这种复杂性在口腔癌(OC)中的转化应用尤其受到欢迎,在口腔癌中,由于侵袭性和致残性手术、高复发率、低生活质量以及诊断后生存率降低,其自然病史令人极其失望。褪黑素激活保护性受体依赖性和非依赖性过程,这些过程可预防组织癌变并抑制肿瘤的恶性进展和转移。相关证据表明,褪黑素的多效性涵盖了通过三种最具特征的表观遗传机制对基因表达的调控:DNA甲基化、染色质修饰和非编码RNA。尽管口腔癌的预后通常不佳,且在过去十年中没有显著的治疗进展记录,但与其他癌症相比,口腔癌受到的关注较少。然而,目前正在进行大量研究工作,以阐明褪黑素的作用机制如何预防导致癌症的表观遗传损伤。鉴于最近的研究结果,全面研究褪黑素可能逆转口腔癌表观遗传异常的生物化学过程,是在患者临床管理方面向前迈出一步的绝佳机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/348b/6895876/be24777c0596/cancers-11-01712-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/348b/6895876/be24777c0596/cancers-11-01712-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/348b/6895876/be24777c0596/cancers-11-01712-g001.jpg

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