Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong.
Expert Rev Mol Diagn. 2012 Sep;12(7):755-65. doi: 10.1586/erm.12.64.
miRNAs are a group of small noncoding RNAs measuring 19-25 nucleotides. Sequence-specific binding of miRNAs to the 3´ untranslated regions of target genes leads to translational repressions. Dysregulation of miRNA expression involved in cancer can be triggered by multiple mechanisms including aberrant DNA methylation of the miRNA gene promoter. Of note, DNA methylation of tumor suppressor miRNAs has been implicated in various human cancers. Moreover, miRNA silencing mediated by aberrant promoter DNA methylation can potentially be reversed by hypomethylating agents, and hence may pose a new therapeutic target in cancer. In this review, the authors will focus on the aberrant methylation of miRNAs in the pathogenesis of lymphoid malignancies including chronic lymphocytic leukemia, multiple myeloma and acute lymphoblastic leukemia.
miRNAs 是一组小的非编码 RNA，长度为 19-25 个核苷酸。miRNAs 通过与靶基因的 3´非翻译区特异性结合，导致翻译抑制。miRNA 表达失调参与癌症的发生，其机制包括 miRNA 基因启动子的异常 DNA 甲基化。值得注意的是，肿瘤抑制 miRNA 的 DNA 甲基化与多种人类癌症有关。此外，异常启动子 DNA 甲基化介导的 miRNA 沉默可以被低甲基化剂逆转，因此可能成为癌症的新治疗靶点。在这篇综述中，作者将重点讨论 miRNA 的异常甲基化在包括慢性淋巴细胞白血病、多发性骨髓瘤和急性淋巴细胞白血病在内的淋巴恶性肿瘤发病机制中的作用。
