Epigenetic regulation of microRNAs in cancer: An integrated review of literature
Epigenetic regulation of microRNAs in cancer: An integrated review of literature
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DOI：
10.1016/j.mrfmmm.2011.03.008
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发表时间：
2011-12-01
影响因子：
2.3
通讯作者：
Calin, George Adrian
中科院分区：
文献类型：
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作者：
Kunej, Tanja;Godnic, Irena;Calin, George Adrian
MicroRNAs （miRNAs）属于异质类非编码rna (ncRNAs)，它调节靶mrna的翻译和降解，控制着大约30%的人类基因。在人类肿瘤中，MiRNA基因可能通过包含或邻近MiRNA基因的CpG岛异常高甲基化和/或组蛋白修饰而沉默。我们对描述表观遗传调控的mirna在癌症中的研究文章进行了文献检索，并确定了2006年至2010年7月间发表的45项研究。来自这些论文的数据是碎片化的，在方法上是异质的，我们的工作代表了对不同信息集整合的第一次系统回顾。本文综述了用于检测miRNA表观遗传调控的方法，包括亚硫酸氢盐基因组测序PCR （BSP）、亚硫酸氢盐pyrosequencing、甲基化特异性PCR （MSP）、亚硫酸氢盐限制性结合分析（COBRA）、甲基化敏感单核苷酸引物延伸（Ms-SNuPE）。MassARRAY技术以及对这些方法的一些改进。这项综合研究揭示了在23种癌症类型中据报道受表观遗传调控的122种mirna。与蛋白质编码基因相比，人类肿瘤基因的甲基化频率高了一个数量级（11.6%；122/1048个已知mirna）。近一半（45%;55/122）的表观遗传调控mirna与不同的癌症类型相关，但另外55%（67/122）的mirna仅存在于一种癌症类型中，因此代表了癌症特异性生物标志物的潜力。数据整合揭示了1q、7q、11q、14q和19q染色体上的miRNA表观基因组热点。对相应的miRNA前体（前miRNA）进行CpG岛分析发现，20%（26/133）的表观遗传调控miRNA在上游5kb范围内存在CpG岛，其中14%（19/133）的miRNA位于CpG岛内。我们的综合调查和分析揭示了候选的癌症特异性miRNA表观遗传特征，这些特征通过靶向miRNA的表观遗传调控为癌症的新治疗策略提供了基础。(C) 2011 Elsevier B.V.版权所有
MicroRNAs (miRNAs) belong to the heterogeneous class of non-coding RNAs (ncRNAs) that regulate the translation and degradation of target mRNAs, and control approximately 30% of human genes. MiRNA genes might be silenced in human tumors (oncomiRs) by aberrant hypermethylation of CpG islands that encompass or lie adjacent to miRNA genes and/or by histone modifications. We performed literature search for research articles describing epigenetically regulated miRNAs in cancer and identified 45 studies that were published between 2006 and 7/2010. The data from those papers are fragmented and methodologically heterogeneous and our work represents first systematic review towards to integration of diverse sets of information.We reviewed the methods used for detection of miRNA epigenetic regulation, which comprise bisulfite genomic sequencing PCR (BSP), bisulfite pyrosequencing, methylation specific PCR (MSP), combined bisulfite restriction analysis (COBRA), methylation sensitive single nucleotide primer extension (Ms-SNuPE). MassARRAY technique and some modifications of those methods. This integrative study revealed 122 miRNAs that were reported to be epigenetically regulated in 23 cancer types. Compared to protein coding genes, human oncomiRs showed an order of magnitude higher methylation frequency (11.6%; 122/1048 known miRNAs). Nearly half, (45%; 55/122) epigenetically regulated miRNAs were associated with different cancer types, but other 55% (67/122) miRNAs were present in only one cancer type and therefore representing cancer-specific biomarker potential. The data integration revealed miRNA epigenomic hot spots on the chromosomes 1q, 7q, 11 q, 14q and 19q. CpG island analysis of corresponding miRNA precursors (pre-miRNAs) revealed that 20% (26/133) of epigenetically regulated miRNAs had a CpG island within the range of 5 kb upstream, among them 14% (19/133) of miRNAs resided within the CpG island. Our integrative survey and analyses revealed candidate cancer-specific miRNA epigenetic signatures which provide the basis for new therapeutic strategies in cancer by targeting the epigenetic regulation of miRNAs. (C) 2011 Elsevier B.V. All rights reserved.