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Genome-Wide Analysis of DNA Methylation and Expression of MicroRNAs in Breast Cancer Cells

机译:乳腺癌细胞中DNA甲基化和microRNA表达的全基因组分析

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DNA methylation of promoters is linked to transcriptional silencing of protein-coding genes, and its alteration plays important roles in cancer formation. For example, hypermethylation of tumor suppressor genes has been seen in some cancers. Alteration of methylation in the promoters of microRNAs (miRNAs) has also been linked to transcriptional changes in cancers; however, no systematic studies of methylation and transcription of miRNAs have been reported. In the present study, to clarify the relation between DNA methylation and transcription of miRNAs, next-generation sequencing and microarrays were used to analyze the methylation and expression of miRNAs, protein-coding genes, other non-coding RNAs (ncRNAs), and pseudogenes in the human breast cancer cell lines MCF7 and the adriamycin (ADR) resistant cell line MCF7/ADR. DNA methylation in the proximal promoter of miRNAs is tightly linked to transcriptional silencing, as it is with protein-coding genes. In protein-coding genes, highly expressed genes have CpG-rich proximal promoters whereas weakly expressed genes do not. This is only rarely observed in other gene categories, including miRNAs. The present study highlights the epigenetic similarities and differences between miRNA and protein-coding genes.
机译:启动子的DNA甲基化与蛋白质编码基因的转录沉默有关,其改变在癌症形成中起重要作用。例如,已经在某些癌症中发现了肿瘤抑制基因的高度甲基化。 microRNA(miRNA)启动子中甲基化的改变也与癌症的转录变化有关。但是,没有关于miRNA甲基化和转录的系统研究的报道。在本研究中,为阐明DNA甲基化与miRNA转录之间的关系,使用下一代测序和微阵列分析了miRNA,蛋白质编码基因,其他非编码RNA(ncRNA)和假基因的甲基化和表达。在人乳腺癌细胞系MCF7和对阿霉素(ADR)耐药的细胞系MCF7 / ADR中具有抗性。 miRNA的近端启动子中的DNA甲基化与转录沉默紧密相连,就像蛋白质编码基因一样。在蛋白质编码基因中,高表达基因具有富含CpG的近端启动子,而弱表达基因则没有。这在包括miRNA在内的其他基因类别中很少见到。本研究突出了miRNA和蛋白质编码基因之间的表观遗传相似性和差异。

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