Zhu Yufu, Qiu Zhichao, Zhang Xiang, Qian Fengyuan, Wang Bin, Wang Lei, Shi Hengliang, Yu Rutong
Insititute of Nervous System Diseases, Xuzhou Medical University, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.
Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.
J Neurooncol. 2017 Jan;131(1):31-39. doi: 10.1007/s11060-016-2279-6. Epub 2016 Sep 17.
Jab1 (Jun activation domain-binding protein 1), also known as CSN5 (COP9 signalosome subunit 5), is frequently overexpressed in several cancer types. However, the biological functions and the molecular mechanisms of the Jab1 protein in human gliomas have not been investigated. In this study, we found that Jab1 protein was increasingly expressed in human glioma tissues comparing with normal brain tissues (Non-tumor). This suggested that Jab1 might be involved in the development of glioma. Thus, the role of Jab1 in glioma cell proliferation was investigated using Jab1 loss- and gain-of-function. The results showed that downregulation of Jab1 significantly inhibited glioma cell proliferation, while overexpression of Jab1 promoted it. Further investigation on molecular targets revealed that silencing of Jab1 obviously increased the p53 protein level thereby promoting the transcription of ubiquitin ligase Siah1 (Seven in absentia homolog 1), which aggravates the degradation of β-catenin. In contrast, overexpression of Jab1 had the opposite effect. Taken together, these findings suggest that Jab1 promotes glioma cell proliferation and increased expression of Jab1 in glioma patients may amplify β-catenin signaling to contribute to glioma cell proliferation.
Jab1（Jun激活结构域结合蛋白1），也被称为CSN5（COP9信号体亚基5），在多种癌症类型中经常过度表达。然而，Jab1蛋白在人类胶质瘤中的生物学功能和分子机制尚未得到研究。在本研究中，我们发现与正常脑组织（非肿瘤组织）相比，Jab1蛋白在人类胶质瘤组织中的表达逐渐增加。这表明Jab1可能参与了胶质瘤的发展。因此，我们利用Jab1功能缺失和功能获得来研究Jab1在胶质瘤细胞增殖中的作用。结果表明，Jab1的下调显著抑制了胶质瘤细胞的增殖，而Jab1的过表达则促进了其增殖。对分子靶点的进一步研究表明，Jab1的沉默明显增加了p53蛋白水平，从而促进了泛素连接酶Siah1（缺失同源物1）的转录，这加剧了β-连环蛋白的降解。相反，Jab1的过表达则产生相反的效果。综上所述，这些发现表明Jab1促进胶质瘤细胞增殖，胶质瘤患者中Jab1表达的增加可能会放大β-连环蛋白信号传导，从而促进胶质瘤细胞增殖。
