Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Wexner Medical Center and Comprehensive Cancer Center, Columbus, OH, USA.
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Wexner Medical Center and Comprehensive Cancer Center, Columbus, OH, USA.
Cancer Lett. 2018 Apr 10;419:96-102. doi: 10.1016/j.canlet.2018.01.013. Epub 2018 Jan 9.
The critical tumor suppressor gene TP53 is either lost or mutated in more than half of human cancers. As an important transcriptional regulator, p53 modulates the expression of many microRNAs. While wild-type p53 uses microRNAs to suppress cancer development, microRNAs that are activated by gain-of-function mutant p53 confer oncogenic properties. On the other hand, the expression of p53 is tightly controlled by a fine-tune machinery including microRNAs. MicroRNAs can target the TP53 gene directly or other factors in the p53 network so that expression and function of either the wild-type or the mutant forms of p53 is downregulated. Therefore, depending on the wild-type or mutant p53 context, microRNAs contribute substantially to suppress or exacerbate tumor development.
抑癌基因 TP53 发生缺失或突变的比例超过半数，是关键的肿瘤抑制基因。作为重要的转录调控因子，p53 可以调节许多 microRNAs 的表达。野生型 p53 通过 microRNAs 抑制癌症的发生，而功能获得性突变型 p53 激活的 microRNAs 则赋予致癌特性。另一方面，p53 的表达受到精细调控机制的严格控制，包括 microRNAs。microRNAs 可以直接靶向 TP53 基因或 p53 网络中的其他因子，从而下调野生型或突变型 p53 的表达和功能。因此，根据野生型或突变型 p53 的情况，microRNAs 可以显著抑制或促进肿瘤的发展。
