Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Adv Exp Med Biol. 2013;774:1-20. doi: 10.1007/978-94-007-5590-1_1.
Mature microRNAs (miRNAs) are single-stranded RNA molecules of 20-23-nucleotide (nt) length that control gene expression in many cellular processes. These molecules typically reduce the translation and stability of mRNAs, including those of genes that mediate processes in tumorigenesis, such as inflammation, cell cycle regulation, stress response, differentiation, apoptosis, and invasion. miRNA targeting is initiated through specific base-pairing interactions between the 5' end ("seed" region) of the miRNA and sites within coding and untranslated regions (UTRs) of mRNAs; target sites in the 3' UTR lead to more effective mRNA destabilization. Since miRNAs frequently target hundreds of mRNAs, miRNA regulatory pathways are complex. To provide a critical overview of miRNA dysregulation in cancer, we first discuss the methods currently available for studying the role of miRNAs in cancer and then review miRNA genomic organization, biogenesis, and mechanism of target recognition, examining how these processes are altered in tumorigenesis. Given the critical role miRNAs play in tumorigenesis processes and their disease specific expression, they hold potential as therapeutic targets and novel biomarkers.
成熟的 microRNAs(miRNAs)是 20-23 个核苷酸(nt)长度的单链 RNA 分子,可控制许多细胞过程中的基因表达。这些分子通常会降低 mRNAs 的翻译和稳定性,包括那些介导肿瘤发生过程的基因,如炎症、细胞周期调节、应激反应、分化、凋亡和侵袭。miRNA 的靶向作用是通过 miRNA 的 5'端(“种子”区域)与 mRNAs 的编码区和非翻译区(UTRs)内的位点之间的特异性碱基配对相互作用来启动的;3'UTR 中的靶位点导致 mRNA 更有效地不稳定。由于 miRNAs 经常靶向数百个 mRNAs,因此 miRNA 调控途径非常复杂。为了对癌症中 miRNA 失调提供批判性概述,我们首先讨论目前用于研究 miRNA 在癌症中作用的方法,然后综述 miRNA 的基因组组织、生物发生和靶标识别机制,研究这些过程在肿瘤发生中是如何改变的。鉴于 miRNAs 在肿瘤发生过程中发挥着关键作用,以及它们在疾病中的特异性表达,它们具有作为治疗靶点和新型生物标志物的潜力。