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

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Abstract

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.

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Acknowledgments

This work was supported by Jiangsu Planned Projects for Postdoctoral Research Funds (1302111B and 1402191C), the China Postdoctoral Science Foundation (2014M551662 and 2016T90507), the National Natural Science Foundation of China (81672490 and 81472345) and the Natural Science Foundation of Jiangsu Province of China (BK20151165).

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    Authors and Affiliations

    1. Insititute of Nervous System Diseases, Xuzhou Medical University, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People’s Republic of China

      Yufu Zhu, Zhichao Qiu, Xiang Zhang, Fengyuan Qian, Bin Wang, Lei Wang, Hengliang Shi & Rutong Yu

    2. Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People’s Republic of China

      Yufu Zhu, Lei Wang, Hengliang Shi & Rutong Yu

    3. The Graduate School, Xuzhou Medical University, Xuzhou, People’s Republic of China

      Zhichao Qiu, Xiang Zhang, Fengyuan Qian & Bin Wang

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    1. Yufu Zhu
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    2. Zhichao Qiu
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    Correspondence to Hengliang Shi or Rutong Yu.

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    Yufu Zhu and Zhichao Qiu have contributed equally to this work.

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    11060_2016_2279_MOESM1_ESM.tif

    Supplementary material 1 Figure 1: (A) Rescue experiment showed the Jab1 shRNA #2 was specific for Jab1. (B and C) EdU assay showed that the shRNA-resistant Jab1 (SR-GFP-Jab1) could abrogate the growth inhibition in the Jab1 shRNA-expressing cells. n.s: no significance, **P < 0.01. (TIF 25502 KB)

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    Zhu, Y., Qiu, Z., Zhang, X. et al. Jab1 promotes glioma cell proliferation by regulating Siah1/β-catenin pathway. J Neurooncol 131, 31–39 (2017). https://doi.org/10.1007/s11060-016-2279-6

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    • DOI: https://doi.org/10.1007/s11060-016-2279-6

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