Stem Cell Program, Children's Hospital Boston, MA 02115, USA.
Trends Cell Biol. 2012 Sep;22(9):474-82. doi: 10.1016/j.tcb.2012.06.001. Epub 2012 Jul 9.
One of the most ancient and highly conserved microRNAs (miRNAs), the let-7 family, has gained notoriety owing to its regulation of stem cell differentiation and essential role in normal development, as well as its tumor suppressor function. Mechanisms controlling let-7 expression have recently been uncovered, specifically the role of the RNA-binding protein Lin28 - a key developmental regulator - in blocking let-7 biogenesis. This review focuses on our current understanding of the Lin28-mediated control of let-7 maturation and highlights the central role of Lin28 in stem cell biology, development, control of glucose metabolism, and dysregulation in human disease. Manipulating the Lin28 pathway for the precise control of let-7 expression may provide novel therapeutic opportunities for cancer and other diseases.
最古老且高度保守的 microRNAs（miRNAs）之一——let-7 家族，因其在干细胞分化中的调控作用及其在正常发育中的重要作用，以及其作为肿瘤抑制因子的功能而声名鹊起。最近已经发现了控制 let-7 表达的机制，特别是 RNA 结合蛋白 Lin28 的作用——Lin28 是关键的发育调节剂——在阻止 let-7 生物发生中的作用。这篇综述重点介绍了我们对 Lin28 介导的 let-7 成熟调控的现有认识，并强调了 Lin28 在干细胞生物学、发育、葡萄糖代谢调控以及人类疾病失调中的核心作用。操纵 Lin28 通路以精确控制 let-7 的表达可能为癌症和其他疾病提供新的治疗机会。
