The mystique of epigenetic regulation: the remarkable case of a human noncoding RNA, nc886

nc886 is a regulatory noncoding RNA that is transcribed by RNA polymerase III (Pol III), is variably expressed in different biological contexts, and plays roles in inflammation and cancer. Epigenetic mechanisms play an intriguing role in regulating nc886 expression. As a maternally imprinted gene and metastable epiallele, nc866 exhibits polymorphic imprinting, with a methylation status that is influenced by environmental and biological factors. Consequently, the promoter DNA methylation status and the different resulting RNA expression levels of nc886 are associated with physiological and pathological conditions. In this review, we summarize the literature and explore the significance in relation to diverse roles of nc886. nc886 is transcribed by RNA polymerase III. nc886 binds to target proteins such as Protein Kinase R and Dicer to control their activities. nc886 has CpG islands in the promoter region, whose hypermethylation suppresses nc886 expression. CpG DNA methylation of nc886 is allele-specific. nc886 is a maternally imprinted gene. Imprinting of nc886 CpG DNA methylation is polymorphic; nc886 is imprinted in 75% of individuals but has both alleles unmethylated in the remaining 25%. nc886 is a metastable epiallele, whose CpG DNA methylation status is stochastically established and largely maintained during development. nc886 CpG DNA methylation in offspring is influenced by maternal factors including nutritional status, folic acid supplementation, age at conception and environmental factors. nc886 CpG DNA methylation is associated with several health traits. nc886 CpG DNA methylation is dysregulated in pathological conditions, with cancer being the most prominent example.nc886是一种由RNA聚合酶III（RNA polymerase III，Pol III）转录的调控性非编码RNA（noncoding RNA），在不同生物学背景下表达水平存在差异，参与炎症反应与癌症发生发展过程。表观遗传调控机制在nc886的表达调控中发挥着引人关注的作用。作为母系印记基因与亚稳态表观等位基因（metastable epiallele），nc886呈现多态性印记特征，其甲基化状态受环境与生物学因素共同影响。因此，nc886启动子区域的DNA甲基化状态及其所导致的不同RNA表达水平，与机体生理及病理状态密切相关。在本综述中，我们对相关研究文献进行系统梳理，并探讨nc886多样化生物学功能的相关意义。nc886可结合蛋白激酶R（Protein Kinase R）、Dicer等靶蛋白，对其活性进行调控。nc886的启动子区域含有CpG岛，该区域的高甲基化会抑制nc886的表达。nc886的CpG DNA甲基化具有等位基因特异性。nc886是母系印记基因，其CpG DNA甲基化印记呈现多态性：75%的个体中nc886存在印记，而剩余25%的个体中两个等位基因均未发生甲基化。nc886属于亚稳态表观等位基因，其CpG DNA甲基化状态随机建立，并在个体发育过程中基本得以维持。子代个体的nc886 CpG DNA甲基化水平受母体因素（包括营养状况、叶酸补充、受孕年龄）以及环境因素的影响。nc886的CpG DNA甲基化与多种健康性状相关。nc886的CpG DNA甲基化在病理状态下存在失调现象，其中以癌症最为典型。