表观遗传调控机制在犬肿瘤中的研究进展

Research Progress on Epigenetic Regulation Mechanism in Canine Tumor

犬肿瘤性疾病是兽医临床上常发的一种疾病,其发病率较高,是造成世界范围内犬死亡的重要原因之一,由于其病理学分类、自发性、基因和信号通路等方面与人类肿瘤有相似之处,可作为人类肿瘤的研究模型。表观遗传是基于DNA序列没有发生改变的情况下所致基因功能和表达水平发生了可遗传的变化,主要通过基因转录或翻译过程的调控,影响其功能和特性。表观遗传改变主要包括DNA甲基化水平改变、组蛋白修饰、染色质重塑和非编码RNA调控等。DNA异常甲基化在犬的多种肿瘤中均有研究,包括犬白血病、淋巴瘤及黑色素瘤等,且犬与人类肿瘤的DNA异常甲基化模式相似。在肿瘤中组蛋白各种修饰酶表达失调,是抗肿瘤药物开发分子靶点研究的主要焦点,但目前在犬肿瘤中的研究较少。非编码RNA中microRNA与lncRNA是目前的研究热点,已有较多研究致力于开发针对非编码RNA的靶向研究药物,但目前在兽医领域应用较少。作者主要综述了犬肿瘤疾病的流行病学、DNA甲基化、组蛋白修饰、非编码RNA等表观遗传学变化在犬肿瘤中的研究进展,揭示表观遗传异常与犬肿瘤发生发展的关系,以期为开发犬肿瘤性疾病诊断、靶向治疗及预后的特异性标志物提供参考依据。

The canine neoplastic disease is common in the veterinary clinic,which has a high incidence and is one of the important causes of dog death worldwide.Because canine tumors are similar to human tumors in their pathological classification,spontaneity,genes,and signal pathways,dogs with tumors can be used as research models for human tumors.Epigenetics refers to heritable changes in gene function and expression levels that occur without a change in DNA sequence,mainly through the regulation of gene transcription and translation process influence the functions and features.Epigenetic changes mainly include changes in DNA methylation level,histone modification,chromatin remolding,and regulation of non-coding RNA.Abnormal DNA methylation has been studied in a variety of canine tumors,including canine leukemia,lymphoma,and melanoma.Among these tumors,the abnormal DNA methylation patterns of canine and human tumors are similar.The dysregulation of the expression of a variety of histone-modifying enzymes in tumors is the research hotspot of molecular targets for the development of anti-tumor drugs,but there are currently few studies in canine tumors.microRNA and lncRNA are currently research focuses on non-coding RNA.Many researches had been devoted to the development of targeted research drugs for non-coding RNA,but currently,there are few applications in the veterinary field.In this paper,the epidemiology,DNA methylation,histone modification,noncoding RNA,and other epigenetic changes in canine cancer were reviewed to reveal the relationship between epigenetic abnormalities and the occurrence and development of canine tumor,and to provide a reference for the development of specific markers for the diagnosis,targeted therapy and prognosis of canine neoplastic diseases.