Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA.
Chin Med J (Engl). 2018 Apr 5;131(7):845-851. doi: 10.4103/0366-6999.228229.
The objective of the study was to summarize the role of DNA methylation in the development and metastasis of uveal melanoma (UM).
The relevant studies in MEDLINE were searched.
In this review, we performed a comprehensive literature search in MEDLINE using "uveal melanoma" AND ("DNA methylation" OR "epigenetics") for original research/review articles published before February 2018 on the relationship between DNA methylation and UM. References of the retrieved studies were also examined to search for potentially relevant papers.
Previous studies on the relationship between DNA methylation and UM covered many genes including tumor suppressor genes (TSGs), cyclin-dependent kinase genes, and other genes. Among them, the TSG genes such as RASSF1A and p16INK4a, which encodes a cyclin-dependent kinase inhibitor, are relatively well-studied genes. Specifically, a high percentage of promoter methylation of RASSF1A was observed in UM cell lines and/or patients with UM. Promoter methylation of RASSF1A was also associated with the development of metastasis. Similarly, a high percentage of promoter hypermethylation of p16INK4a was found in UM cell lines. DNA promoter methylation can control the expression of p16INK4a, which affect cell growth, migration, and invasion in UM. Many other genes might also be involved in the pathogenesis of UM such as the Ras and EF-hand domain containing (RASEF) gene, RAB31, hTERT, embryonal fyn-associated substrate, and deleted in split-hand/split-foot 1.
Our review reveals the complex mechanisms underlying the tumorigenesis of UM and highlights the great needs of future studies to discover more genes/5'-C-phosphate-G-3' sites contributing to the development/metastasis of UM and explore the mechanisms through which epigenetic changes exert their function in UM.
本研究旨在总结 DNA 甲基化在葡萄膜黑色素瘤（UM）发生和转移中的作用。
在 MEDLINE 中搜索相关研究。
在本综述中，我们使用“葡萄膜黑色素瘤”和（“DNA 甲基化”或“表观遗传学”）在 MEDLINE 中进行了全面的文献检索，以搜索 2018 年 2 月之前发表的关于 DNA 甲基化与 UM 之间关系的原始研究/综述文章。还检查了检索研究的参考文献，以搜索潜在相关的论文。
先前关于 DNA 甲基化与 UM 之间关系的研究涵盖了许多基因，包括肿瘤抑制基因（TSGs）、细胞周期蛋白依赖性激酶基因和其他基因。其中，RASSF1A 和 p16INK4a 等 TSG 基因，其编码细胞周期蛋白依赖性激酶抑制剂，是研究较为充分的基因。具体而言，在 UM 细胞系和/或 UM 患者中观察到 RASSF1A 的启动子高甲基化。RASSF1A 启动子甲基化也与转移的发生有关。同样，在 UM 细胞系中也发现了 p16INK4a 的启动子高甲基化。DNA 启动子甲基化可以控制 p16INK4a 的表达，从而影响 UM 中的细胞生长、迁移和侵袭。许多其他基因也可能参与 UM 的发病机制，如 Ras 和 EF-hand 结构域包含（RASEF）基因、RAB31、hTERT、胚胎 fyn 相关底物和分裂手/分裂足 1 缺失。
我们的综述揭示了 UM 发生的复杂机制，并强调了未来研究发现更多基因/5'-C-磷酸-G-3' 位点有助于 UM 的发展/转移的巨大需求，并探讨了表观遗传变化在 UM 中发挥作用的机制。
