DLK1-DIO3印记区域的miRNAs与疾病的发生

The miRNAs Within The DLK1-DIO3 Imprinted Region Involved in Disease Pathogenesis

哺乳动物的基因组以发育调控模式进行转录,生成长的和短的非编码RNAs(non-coding RNA,ncRNAs).ncRNAs占到人类转录组的98%,与生物体进化复杂程度显著相关.MicroRNAs(miRNAs)是目前研究比较透彻的,长度大约为20~24个核苷酸的ncRNAs,其通过与靶基因mRNA的结合在转录后水平负调控基因的表达.人类基因组中一个最大的miRNA簇位于14号染色体(14q32)的DLK1-DIO3印记区域,包括了54个miRNAs.这些miRNAs通过参与调节重要的信号通路在许多病理过程中发挥作用.充分了解DLK1-DIO3印记区域中这个大的miRNA簇,在病理生理过程中的重要性将有助于为相关疾病的治疗提供新的策略.本文比较深入地分析了DLK1-DIO3印记区域中的miRNAs在调控组织动态平衡以及多种癌症发生中的作用,同时对其潜在的临床应用价值进行了讨论.

The mammalian genome is transcribed in a developmentally regulated manner, generating RNA transcripts ranging from long to short non-coding RNA（ncRNAs）. NcRNAs represent up to 98% of the human transcriptome and have an association with organism complexity. MiRNAs are the best-studied class of ncRNAs.MiRNAs are approximately 22 nucleotides long and act as gene negative regulators at a post-transcription level. In humans, the DLK1-DIO3 genomic region, located on human chromosome 14（14q32）, contains one of the largest microRNA clusters with 54 miRNAs in the genome. Many of these miRNAs are differentially expressed by modulating important signaling pathways in several pathologic processes and various cancers. A better understanding of the pathophysiologic importance of the DLK1-DIO3 domain-containing microRNA cluster may contribute to innovative therapeutic strategies in a range of diseases. Here we present an in-depth review of the role the microRNAs of DLK1-DIO3 region may play in controlling tissue homeostasis and in the pathogenesis of mostly cancer. The potential clinical implications of these miRNAs are also discussed.