Yang Zhen, Xu Feng, Teschendorff Andrew E, Zhao Yi, Yao Lei, Li Jian, He Yungang
Center for Medical Research and Innovation of Pudong Hospital, The Shanghai Key Laboratory of Medical Epigenetics, International Co-Laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Front Mol Biosci. 2022 Dec 2;9:1067406. doi: 10.3389/fmolb.2022.1067406. eCollection 2022.
DNA methylation is one of the most important epigenetic mechanisms that governing regulation of gene expression, aberrant DNA methylation patterns are strongly associated with human malignancies. Long non-coding RNAs (lncRNAs) have being discovered as a significant regulator on gene expression at the epigenetic level. Emerging evidences have indicated the intricate regulatory effects between lncRNAs and DNA methylation. On one hand, transcription of lncRNAs are controlled by the promoter methylation, which is similar to protein coding genes, on the other hand, lncRNA could interact with enzymes involved in DNA methylation to affect the methylation pattern of downstream genes, thus regulating their expression. In addition, circular RNAs (circRNAs) being an important class of noncoding RNA are also found to participate in this complex regulatory network. In this review, we summarize recent research progress on this crosstalk between lncRNA, circRNA, and DNA methylation as well as their potential functions in complex diseases including cancer. This work reveals a hidden layer for gene transcriptional regulation and enhances our understanding for epigenetics regarding detailed mechanisms on lncRNA regulatory function in human cancers.
DNA甲基化是调控基因表达的最重要的表观遗传机制之一，异常的DNA甲基化模式与人类恶性肿瘤密切相关。长链非编码RNA（lncRNAs）已被发现是表观遗传水平上基因表达的重要调节因子。新出现的证据表明lncRNAs与DNA甲基化之间存在复杂的调控作用。一方面，lncRNAs的转录受启动子甲基化的控制，这与蛋白质编码基因类似；另一方面，lncRNA可与参与DNA甲基化的酶相互作用，影响下游基因的甲基化模式，从而调控其表达。此外，环状RNA（circRNAs）作为一类重要的非编码RNA，也被发现参与了这一复杂的调控网络。在这篇综述中，我们总结了lncRNA、circRNA与DNA甲基化之间相互作用的最新研究进展，以及它们在包括癌症在内的复杂疾病中的潜在功能。这项工作揭示了基因转录调控的一个隐藏层面，并增强了我们对表观遗传学中lncRNA在人类癌症中调控功能详细机制的理解。
