INSERM, U836, Team7 Nanomedicine and Brain, BP 170, Grenoble, France.
Front Biosci (Landmark Ed). 2012 Jun 1;17(7):2508-40. doi: 10.2741/4068.
microRNAs (miRNAs) are small noncoding endogenously produced RNAs that play key roles in controlling the expression of many cellular proteins. Once they are recruited and incorporated into a ribonucleoprotein complex miRISC, they can target specific mRNAs in a miRNA sequence-dependent process and interfere in the translation into proteins of the targeted mRNAs via several mechanisms. Consequently, miRNAs can regulate many cellular pathways and processes. Dysregulation of their physiological roles may largely contribute to disease. In particular, in cancer, miRNAs can be involved in the deregulation of the expression of important genes that play key roles in tumorigenesis, tumor development, and angiogenesis and have oncogenic or tumor suppressor roles. This review focuses on the biogenesis and maturation of miRNAs, their mechanisms of gene regulation, and the way their expression is deregulated in cancer. The involvement of miRNAs in several oncogenic pathways such as angiogenesis and apoptosis, and in the inter-cellular dialog mediated by miRNA-loaded exosomes as well as the development of new therapeutical strategies based on miRNAs will be discussed.
microRNAs (miRNAs) 是小型内源性非编码 RNA，在控制许多细胞蛋白的表达中发挥关键作用。一旦它们被招募并整合到核糖核蛋白复合物 miRISC 中，它们就可以通过 miRNA 序列依赖性过程靶向特定的 mRNAs，并通过几种机制干扰靶向 mRNAs 的翻译为蛋白质。因此，miRNAs 可以调节许多细胞途径和过程。它们生理作用的失调可能在很大程度上导致疾病。特别是在癌症中，miRNAs 可能参与调节重要基因的表达失调，这些基因在肿瘤发生、肿瘤发展和血管生成中发挥关键作用，具有致癌或肿瘤抑制作用。本文重点介绍了 miRNAs 的生物发生和成熟、它们的基因调控机制以及在癌症中表达失调的方式。将讨论 miRNAs 在血管生成和细胞凋亡等几种致癌途径中的作用，以及由 miRNA 负载的外泌体介导的细胞间对话，以及基于 miRNA 的新治疗策略的发展。
