Wang Yangming, Blelloch Robert
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143, USA.
Cancer Res. 2009 May 15;69(10):4093-6. doi: 10.1158/0008-5472.CAN-09-0309. Epub 2009 May 12.
The cell cycle is tightly orchestrated during normal development. Embryonic stem (ES) cells have a unique cell cycle structure, in which the G1/S restriction is largely absent, enabling cells to rapidly move through the G1 phase and enter the S phase. This hastened cell cycle allows the early embryo to rapidly grow. Recent experiments suggest that small noncoding RNAs, the microRNAs (miRNAs), play a central role in achieving this unique cell cycle structure. The responsible miRNAs function by suppressing multiple inhibitors of the G1/S transition. Expression of these miRNAs drops dramatically as the ES cells differentiate and as the G1 phase extends. Some of the same miRNAs are overexpressed in cancers, in which they can promote tumor growth, suggesting common mechanisms of miRNA-regulated cell cycle control in ES cells and cancers. This review discusses these recent findings in the context of broader knowledge of cell cycle control in normal and abnormal development.
在正常发育过程中,细胞周期受到严格调控。胚胎干细胞(ES细胞)具有独特的细胞周期结构,其中G1/S限制基本不存在,使细胞能够快速通过G1期并进入S期。这种加速的细胞周期使早期胚胎能够快速生长。最近的实验表明,小非编码RNA,即微小RNA(miRNA),在实现这种独特的细胞周期结构中起着核心作用。起作用的miRNA通过抑制G1/S转换的多种抑制剂来发挥功能。随着ES细胞分化以及G1期延长,这些miRNA的表达会急剧下降。一些相同的miRNA在癌症中过度表达,它们可促进肿瘤生长,这表明在ES细胞和癌症中miRNA调控细胞周期的机制具有共性。本综述在正常和异常发育中细胞周期调控的更广泛知识背景下讨论了这些最新发现。