Xiong Jianjun, Xu Xiaoyuan, Zhou Xiaou, Liu Jianyun, Gong Zhen, Wu Ping, Li Weidong
Jiangxi Province Key Laboratory of Systems Biomedicine, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China.
College of Basic Medical Science, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China.
Mol Med Rep. 2014 Dec;10(6):3343-7. doi: 10.3892/mmr.2014.2666. Epub 2014 Oct 15.
The ubiquitin‑specific protease 22 (USP22) gene is overexpressed in the majority of types of cancer cells, and has been implicated in tumorigenesis. However, the mechanisms that regulate its expression remain unclear. The results of the present study demonstrated that the expression of USP22 is negatively regulated by trichostatin A (TSA), a classical histone deacetylase inhibitor. Furthermore, TSA was revealed to interfere with the binding of RNA polymerase II to the USP22 promoter, directly suppressing its transcription. In addition, the overexpression of USP22 was observed to attenuate TSA‑induced apoptosis in HeLa cells. To the best of our knowledge, these results provide the first insight into the regulation of the USP22 gene by antitumor drugs and into the mechanisms underlying the anticancer activity of TSA.
泛素特异性蛋白酶22(USP22)基因在大多数类型的癌细胞中过表达,并与肿瘤发生有关。然而,调节其表达的机制仍不清楚。本研究结果表明,USP22的表达受到曲古抑菌素A(TSA)的负调控,TSA是一种经典的组蛋白去乙酰化酶抑制剂。此外,TSA被发现会干扰RNA聚合酶II与USP22启动子的结合,直接抑制其转录。此外,观察到USP22的过表达减弱了TSA诱导的HeLa细胞凋亡。据我们所知,这些结果首次揭示了抗肿瘤药物对USP22基因的调控以及TSA抗癌活性的潜在机制。