Hata Akiko, Kashima Risa
a Cardiovascular Research Institute, University of California , San Francisco , CA , USA.
Crit Rev Biochem Mol Biol. 2016 May-Jun;51(3):121-34. doi: 10.3109/10409238.2015.1117054. Epub 2015 Dec 1.
MicroRNAs (miRNAs) are integral to the gene regulatory network. A single miRNA is capable of controlling the expression of hundreds of protein coding genes and modulate a wide spectrum of biological functions, such as proliferation, differentiation, stress responses, DNA repair, cell adhesion, motility, inflammation, cell survival, senescence and apoptosis, all of which are fundamental to tumorigenesis. Overexpression, genetic amplification, and gain-of-function mutation of oncogenic miRNAs ("onco-miRs") as well as genetic deletion and loss-of-function mutation of tumor suppressor miRNAs ("suppressor-miRs") are linked to human cancer. In addition to the dysregulation of a specific onco-miR or suppressor-miRs, changes in global miRNA levels resulting from a defective miRNA biogenesis pathway play a role in tumorigenesis. The function of individual onco-miRs and suppressor-miRs and their target genes in cancer has been described in many different articles elsewhere. In this review, we primarily focus on the recent development regarding the dysregulation of the miRNA biogenesis pathway and its contribution to cancer.
微小RNA(miRNA)是基因调控网络不可或缺的一部分。单个miRNA能够控制数百个蛋白质编码基因的表达,并调节广泛的生物学功能,如增殖、分化、应激反应、DNA修复、细胞黏附、迁移、炎症、细胞存活、衰老和凋亡,所有这些都是肿瘤发生的基础。致癌miRNA(“致癌miR”)的过表达、基因扩增和功能获得性突变以及肿瘤抑制miRNA(“抑制miR”)的基因缺失和功能丧失性突变都与人类癌症有关。除了特定致癌miR或抑制miR的失调外,有缺陷的miRNA生物合成途径导致的整体miRNA水平变化也在肿瘤发生中起作用。许多不同的文章已在其他地方描述了个体致癌miR和抑制miR及其靶基因在癌症中的功能。在本综述中,我们主要关注miRNA生物合成途径失调的最新进展及其对癌症的影响。