Dykxhoorn Derek M, Chowdhury Dipanjan, Lieberman Judy
Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Adv Exp Med Biol. 2008;615:299-329. doi: 10.1007/978-1-4020-6554-5_14.
The endogenous RNA interference (RNAi) pathway regulates cellular differentiation and development using small noncoding hairpin RNAs, called microRNAs. This chapter will review the link between mammalian microRNAs and genes involved in cellular proliferation, differentiation, and apoptosis. Some microRNAs act as oncogenes or tumor suppressor genes, but the target gene networks they regulate are just beginning to be described. Cancer cells have altered atterns of microRNA expression, which can be used to identify the cell of origin and to subtype cancers. RNAi has also been used to identify novel genes involved in cellular transformation using forward genetic screening methods previously only possible in invertebrates. Possible strategies and obstacles to harnessing RNAi for cancer therapy will also be discussed.
内源性RNA干扰(RNAi)途径利用称为微小RNA的小型非编码发夹RNA来调节细胞分化和发育。本章将综述哺乳动物微小RNA与参与细胞增殖、分化和凋亡的基因之间的联系。一些微小RNA起着癌基因或肿瘤抑制基因的作用,但它们所调控的靶基因网络才刚刚开始被描述。癌细胞具有改变的微小RNA表达模式,这可用于识别肿瘤起源细胞和对癌症进行亚型分类。RNAi也已被用于通过正向遗传学筛选方法来鉴定参与细胞转化的新基因,而这种方法以前仅在无脊椎动物中可行。还将讨论利用RNAi进行癌症治疗的可能策略和障碍。