肿瘤细胞中肿瘤特异性 DNA 高甲基化沉默的抑瘤 microRNA。
Tumor-suppressive microRNA silenced by tumor-specific DNA hypermethylation in cancer cells.
机构信息
Department of Molecular Cytogenetics, Tokyo Medical and Dental University, Tokyo, Japan.
出版信息
Cancer Sci. 2012 May;103(5):837-45. doi: 10.1111/j.1349-7006.2012.02236.x. Epub 2012 Mar 13.
Abstract
MicroRNA (miRNA) genes, located in intergenic or intragenic non-coding regions of the genome, are transcribed and processed to small non-protein-coding RNA of approximately 22 nucleotides negatively regulating gene expression. Some miRNA have already been reported for their genetic alterations, aberrant expression and oncogenic or tumor-suppressive functions. After 2008, there has been a striking increase in the number of publications reporting tumor-suppressive miRNA (TS-miRNA) silenced epigenetically in various types of cancers, suggesting important clinical applications for miRNA-based molecular diagnosis and therapy for cancers. Here, we introduce a correlation of the gene silencing of TS-miRNA through CpG island hypermethylation with the genomic distances between intergenic and intragenic miRNA genes or protein-coding host genes and CpG islands located around these genes. Furthermore, we also discuss the potential of miRNA replacement therapy for cancers using double-stranded RNA mimicking TS-miRNA.
摘要
MicroRNA (miRNA) 基因位于基因组的基因间或基因内非编码区，转录并加工为大约 22 个核苷酸的小非蛋白编码 RNA，负向调节基因表达。一些 miRNA 已被报道存在遗传改变、异常表达以及致癌或抑癌功能。2008 年后，大量报道表明，在各种类型的癌症中，肿瘤抑制 miRNA（TS-miRNA）通过表观遗传沉默，提示 miRNA 为基础的分子诊断和癌症治疗具有重要的临床应用价值。在这里，我们通过 CpG 岛过度甲基化与基因间和基因内 miRNA 基因或蛋白质编码宿主基因与位于这些基因周围的 CpG 岛之间的基因组距离，介绍了 TS-miRNA 基因沉默的相关性。此外，我们还讨论了使用双链 RNA 模拟 TS-miRNA 进行癌症 miRNA 替代治疗的潜力。
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