Role of CTCF in the regulation of microRNA expression.
Role of CTCF in the regulation of microRNA expression.
复制标题
DOI：
10.3389/fgene.2012.00186
复制
发表时间：
2012
影响因子：
3.7
通讯作者：
Saito H
中科院分区：
文献类型：
--
作者：
Saito Y;Saito H
MicroRNAs(MiRNAs)是一种调节各种靶基因表达的非编码小RNA。MiRNAs以组织特异性的方式表达，在细胞增殖、凋亡和分化中发挥重要作用。表观遗传改变，如DNA甲基化和组蛋白修饰，对于染色质重塑和包括miRNAs在内的基因表达调控是必不可少的。CCCTC结合因子CTCF是已知的与绝缘体结合的因子，具有增强子阻断和屏障功能，最近，它还对基因组的三维组织做出了贡献。CTCF还可以作为一种屏障，阻止DNA甲基化和组蛋白抑制标记在肿瘤抑制基因启动子区的扩散。最近的研究表明，CTCF还参与了癌细胞和干细胞中miR-125b1、miR-375和miR-290簇等miRNAs的调控。MiR-125b1是一种候选的肿瘤抑制因子，在乳腺癌细胞中被沉默。另一方面，miR-375可能具有致癌作用，并且在乳腺癌细胞中过表达。CTCF参与miR-125b1和miR-375的调控，表明存在多种与CTCF相关的miRNAs表观遗传调控模式。CTCF也可能通过对miR-290簇的调节在细胞的多能性中发挥关键作用。这些观察结果表明，CTCF介导的miRNAs调控可能是癌症治疗和再生医学的一种新方法。
MicroRNAs (miRNAs) are small non-coding RNAs that regulate expression of various target genes. miRNAs are expressed in a tissue-specific manner and play important roles in cell proliferation, apoptosis, and differentiation. Epigenetic alterations such as DNA methylation and histone modification are essential for chromatin remodeling and regulation of gene expression including miRNAs. The CCCTC-binding factor, CTCF, is known to bind insulators and exhibits an enhancer-blocking and barrier function, and more recently, it also contributes to the three-dimensional organization of the genome. CTCF can also serve as a barrier against the spread of DNA methylation and histone repressive marks over promoter regions of tumor suppressor genes. Recent studies have shown that CTCF is also involved in the regulation of miRNAs such as miR-125b1, miR-375, and the miR-290 cluster in cancer cells and stem cells. miR-125b1 is a candidate of tumor suppressor and is silenced in breast cancer cells. On the other hand, miR-375 may have oncogenic function and is overexpressed in breast cancer cells. CTCF is involved in the regulation of both miR-125b1 and miR-375, indicating that there are various patterns of CTCF-associated epigenetic regulation of miRNAs. CTCF may also play a key role in the pluripotency of cells through the regulation of miR-290 cluster. These observations suggest that CTCF-mediated regulation of miRNAs could be a novel approach for cancer therapy and regenerative medicine.