Frenzel Anna, Lovén Jakob, Henriksson Marie Arsenian
Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
Genes Cancer. 2010 Jun;1(6):660-7. doi: 10.1177/1947601910377488.
The MYC protein controls many cellular processes, including proliferation, cell cycle progression, cell growth, metabolism, angiogenesis, differentiation, cell adhesion, and motility. This is primarily achieved through transcriptional regulation of large gene networks that ultimately results in activation or repression of target genes. Given its broad regulatory scope, the expression of the MYC gene itself needs to be tightly controlled. Deregulation of MYC expression promotes tumorigenesis and, not surprisingly, MYC is frequently activated in many different human cancers. Furthermore, these tumors become highly dependent on sustained MYC expression, while MYC inactivation results in desirable anticancer effects, such as cell death, differentiation, and/or senescence. Thus, MYC has emerged as an attractive target for cancer therapy. In addition to regulating protein-coding genes, MYC also governs the expression of microRNAs, many of which have important regulatory roles in cancer development and progression. Here we will discuss how MYC-regulated miRNAs could be exploited for therapeutic development for cancer.
MYC蛋白控制许多细胞过程,包括增殖、细胞周期进程、细胞生长、代谢、血管生成、分化、细胞黏附和运动。这主要是通过对大型基因网络的转录调控来实现的,最终导致靶基因的激活或抑制。鉴于其广泛的调控范围,MYC基因本身的表达需要受到严格控制。MYC表达失调会促进肿瘤发生,不出所料,MYC在许多不同的人类癌症中经常被激活。此外,这些肿瘤变得高度依赖于MYC的持续表达,而MYC失活则会产生理想的抗癌效果,如细胞死亡、分化和/或衰老。因此,MYC已成为癌症治疗的一个有吸引力的靶点。除了调节蛋白质编码基因外,MYC还控制微小RNA的表达,其中许多微小RNA在癌症发展和进程中具有重要的调控作用。在这里,我们将讨论如何利用MYC调控的微小RNA进行癌症治疗开发。