Roush Sarah, Slack Frank J
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Trends Cell Biol. 2008 Oct;18(10):505-16. doi: 10.1016/j.tcb.2008.07.007. Epub 2008 Sep 4.
The first two known microRNAs (miRNAs), lin-4 and let-7, were originally discovered in the nematode Caenorhabditis elegans and control the timing of stem-cell division and differentiation. let-7 was subsequently found as the first known human miRNA. let-7 and its family members are highly conserved across species in sequence and function, and misregulation of let-7 leads to a less differentiated cellular state and the development of cell-based diseases such as cancer. Although much research has been devoted to let-7 target prediction and to understanding its biological role, research into what regulates let-7 has only just begun. Here, we review let-7-family conservation and the recent advances in understanding how let-7-expression is regulated at the transcriptional and post-transcriptional levels across species. A greater understanding of what controls let-7 expression might enable the development of treatments to fight or prevent many cancers.
最初发现的两种已知的微小RNA（miRNA），即lin-4和let-7，最初是在秀丽隐杆线虫中发现的，它们控制干细胞分裂和分化的时间。随后，let-7被发现是首个已知的人类miRNA。let-7及其家族成员在物种间的序列和功能上高度保守，let-7的调控异常会导致细胞分化程度降低，并引发诸如癌症等基于细胞的疾病。尽管已经有大量研究致力于let-7的靶标预测以及理解其生物学作用，但对let-7调控机制的研究才刚刚起步。在此，我们综述了let-7家族的保守性，以及近期在理解跨物种let-7表达在转录和转录后水平如何调控方面取得的进展。更深入地了解调控let-7表达的因素可能有助于开发对抗或预防多种癌症的治疗方法。
