小RNA在血液肿瘤研究中应用的新进展

Recent Advances on Application of Small RNA in Research for Hematological Malignancies ——Review

小RNA包括siRNA和miRNA两种,前者是伴随着RNAi现象发现的,是对外源基因剪切加工形成的,是生物维持自身基因组稳定性的一种机制。而miRNA是基因组中固有的,是在转录后水平调节基因表达的重要机制。小RNA的作用方式有两种:介导目标RNA降解和抑制蛋白质翻译。前者要求小RNA与目标RNA精确互补,而后者只要求部分互补,采取何种机制取决于互补程度而不是其来源。RNAi作为下调基因表达的手段,在功能基因组学中已有广泛的应用。对血液肿瘤发病相关基因,尤其对染色体易位造成的相关融合基因、凋亡相关基因及多药耐药基因的干扰研究表明,该技术不但是研究机制的有力手段,而且具有临床应用前景。对microRNA的研究发现,它在多种血液肿瘤如多种淋巴瘤和白血病中存在表达的变化,并与多种癌基因相关,提示它广泛参与血液肿瘤的发病机制。本文就RNA干扰和小RNA的发现和作用,以及小RNA在血液肿瘤研究中的应用作一综述。

The small RNAs include siRNA and miRNA. SiRNA is the splicing product of exogeneous dsRNA by which to keep genome stability, while miRNA are processed from endogenous genome and work as a post - transcriptional regulator for gene expression. The small RNAs act in two ways ： mediate degradation of of target RNA and inhibit translation of protein. The former requires the accurate complementation between small RNA and target RNA, while the latter requires only partial complementation. Which mechanism used depends on complementation degree, but not their origins. The RNAi as a technique for down - regulating target gene expression has been widly used in functional genomic studies and hematologic studies, especially for translocation - related fusion gene, apoptosis - related gene and MDR gene in leukemia. The results show that RNAi technique not only is the powerful tool for study mechanism but also has therapeutic potentials in clinic. Some studies reveal that changes of miRNA expression exist in many hematological malignancies and relate to known oncogenes, which indicates the miRNA is involved in pathogenesis of these diseases. This article reviews the discovery and effect of RNAi and small RNAs, as well as the similarities and differencies between siRNA and miRNA, and focuses on the research of small RNAs in hematological malignancies.