Jab1 promotes glioma cell proliferation by regulating Siah1/β-catenin pathway

详细信息    查看全文

• 作者：Yufu Zhu ; Zhichao Qiu ; Xiang Zhang ; Fengyuan Qian ; Bin Wang…
• 关键词：Glioma ; Jab1 ; P53 ; Siah1 ; β ; Catenin
• 刊名：Journal of Neuro-Oncology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：131
• 期：1
• 页码：31-39
• 全文大小：
• 刊物类别：Medicine
• 刊物主题：Oncology; Neurology;
• 出版者：Springer US
• ISSN：1573-7373
• 卷排序：131

文摘

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.