microRNA 在诱导体细胞重编程中的作用

摘要

microRNA 是调控基因转录后水平的一类长度约为22 个核苷酸的非编码小分子RNA.大量研究证实,microRNAs 广泛分布于真核生物,其在细胞的分化发育、生长代谢等各种活动中都起着重要的调节作用.诱导多能性干细胞(Induced pluripotent stem cell,iPS)是将体细胞诱导成为具有胚胎干细胞性质的多潜能干细胞.iPS过程的核心为体细胞表观遗传状态发生重编程,因此,探明体细胞重编程机制对建立完善的iPS 技术具有重要理论和实际意义.利用病毒载体将Oct4、Sox2、Klf4 和c-Myc 等因子导入体细胞的方法已不断发展,但"基因组整合"及原癌基因的参与增加了诱导细胞的致癌率.随着使用腺病毒、质粒或蛋白诱导等"非整合型"方法及L-myc 的替换均可获得具有多潜能性的干细胞,癌变的风险大大降低.但其发生的理论机制仍不十分清楚.最近的研究证实,microRNAs 影响体细胞的重编程过程,特别是miR302/367、miR200、miR-34 和miR290/295等家族的microRNAs 在体细胞诱导为iPS 过程中发挥重要作用.文章就近年microRNA 在诱导多能干细胞中的作用进行综述.%MicroRNAs are -22 nt long small noncoding RNA molecules that silence post-transcription gene expression. It has proven that microRNAs are widely expressed in eukaryotes and play an important role in the regulation of cell differentiation and development, growth metabolism, and many other cell activities. Induced pluripotent stem cells (iPS) are a type of pluripotent stem cells reprogrammed from somatic cells and exhibit the essential characteristics of embryonic stem cells. iPS technology has been widely applied in the biological and medical fields, and the key of it is reprogramming of somatic epigenetic state. Therefore, it is of important theoretical and practical significance to study the mechanisms of somatic reprogramming for establishment of an improved iPS technology. The methods of transfection of defined exogenetic stem factors, such as Oct4, Sox2, Klf4, and c-Myc into somatic cells through viral vectors have been continuously improving, but the genome integration and reactivation of the oncogenic gene increase the tumorigenicity of induced cells. The integra-tion-fiee ways, such as adenovirus, plasmid, recombinant proteins, and L-myc replacement used in iPS technology signifi-rn cantly reduce the risk of cancer. However, the inducing mechanisms are still unclear. Recent studies showed that microRNA affect the process of somatic cell reprogramming, especially embryonic stem cell regulating (ESCC) family of microRNAs (miR302/367, miR200, miR-34, and miR290/295) enhances the reprogramming of embryonic fibroblasts to iPS. This articlernreviews the recent progresses of roles of microRNA in iPS.