Center for Genomic Science of IIT@CGS, Fondazione Istituto Italiano di Tecnologia (IIT), 20139 Milan, Italy.
Int J Mol Sci. 2021 Jun 8;22(12):6168. doi: 10.3390/ijms22126168.
MYC is a transcription factor that controls the expression of a large fraction of cellular genes linked to cell cycle progression, metabolism and differentiation. MYC deregulation in tumors leads to its pervasive genome-wide binding of both promoters and distal regulatory regions, associated with selective transcriptional control of a large fraction of cellular genes. This pairs with alterations of cell cycle control which drive anticipated S-phase entry and reshape the DNA-replication landscape. Under these circumstances, the fine tuning of DNA replication and transcription becomes critical and may pose an intrinsic liability in MYC-overexpressing cancer cells. Here, we will review the current understanding of how MYC controls DNA and RNA synthesis, discuss evidence of replicative and transcriptional stress induced by MYC and summarize preclinical data supporting the therapeutic potential of triggering replicative stress in MYC-driven tumors.
MYC 是一种转录因子，可控制与细胞周期进程、代谢和分化相关的大部分细胞基因的表达。肿瘤中 MYC 的失调导致其在整个基因组上普遍结合启动子和远端调控区域，与大部分细胞基因的选择性转录调控相关。这与细胞周期控制的改变相配对，这些改变驱动预期的 S 期进入并重塑 DNA 复制景观。在这种情况下，DNA 复制和转录的精细调节变得至关重要，并且可能在 MYC 过表达的癌细胞中构成内在的缺陷。在这里，我们将回顾当前对 MYC 如何控制 DNA 和 RNA 合成的理解，讨论由 MYC 诱导的复制和转录应激的证据，并总结支持在 MYC 驱动的肿瘤中引发复制应激的治疗潜力的临床前数据。
