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TSG101 Promotes the Proliferation, Migration, and Invasion of Human Glioma Cells by Regulating the AKT/GSK3β/β-Catenin and RhoC/Cofilin Pathways

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Abstract

The tumor susceptibility gene 101 (TSG101) has been reported to play important roles in the development and progression of several human cancers, such as pancreatic cancer, prostate cancer, and hepatocellular carcinoma. However, its potential roles and underlined mechanisms in human glioma are still needed to be further clarified. This study was designed to assess the expression of TSG101 in glioma patients and its effects on glioma cell proliferation, migration, and invasion. Publicly available data revealed that TSG101 mRNA was significantly upregulated in glioma tissues, and high levels of TSG101 were associated with poor prognosis in glioma patients. Western blot and immunohistochemistry experiments further showed that the expression level of TSG101 protein was significantly upregulated in glioma patients, especially in the patients with high-grade glioma. The functional studies showed that knockdown of TSG101 suppressed the proliferation, migration, and invasion of glioma cells, while overexpression of TSG101 facilitated them. Mechanistic studies indicated that the proliferation, migration, and invasion induced by TSG101 in human glioma were related to AKT/GSK3β/β-catenin and RhoC/Cofilin signaling pathways. In conclusion, the above results suggest that the expression of TSG101 is elevated in glioma patients, which accelerates the proliferation, migration, and invasion of glioma cells by regulating the AKT/GSK3β/β-catenin and RhoC/Cofilin pathways.

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Data Availability

The datasets supporting the conclusions of this article are included within the article and its additional files.

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Funding

This work was supported by the National Natural Science Foundation of China (81672490 and 81874081), the Natural Science Foundation of Jiangsu Province of China (BK20181149), the Foundation of Xuzhou Science and Technology Bureau (KC20139), the Jiangsu Provincial Qing Lan Project and Jiangsu Provincial Medical Youth Talent (QNRC2016784), and the Young Science and Technology Innovation Team of Xuzhou Medical University Key Research and Development Plan of Jiangsu Province (TD202006).

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  1. Yufu Zhu and Yang Xu contributed equally to this work.

Authors and Affiliations

  1. Institute of Nervous System Diseases, the Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, 84 West Huai-Hai Road, Xuzhou, 221002, Jiangsu, People’s Republic of China

    Yufu Zhu, Yang Xu, Tianze Chen, Qiang Ma, Sunil Rauniyar, Lei Wang & Hengliang Shi

  2. Central Laboratory, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China

    Hengliang Shi

  3. Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China

    Hengliang Shi

  4. Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, China

    Yujian Zhang

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  1. Yufu Zhu
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  3. Tianze Chen
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Contributions

YZ and YX performed the experimental procedures. TC and YZ constructed the plasmids. QM, SR, and LW assisted in the data analysis. HS designed and wrote the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hengliang Shi.

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The experimental protocol for animal studies was reviewed and approved by the Ethics Committee of Xuzhou Medical University. Human glioma tissues were obtained from the Affiliated Hospital of Xuzhou Medical University. This study was approved by the Ethics Committee of the Affiliated Hospital of Xuzhou Medical University.

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Zhu, Y., Xu, Y., Chen, T. et al. TSG101 Promotes the Proliferation, Migration, and Invasion of Human Glioma Cells by Regulating the AKT/GSK3β/β-Catenin and RhoC/Cofilin Pathways. Mol Neurobiol 58, 2118–2132 (2021). https://doi.org/10.1007/s12035-020-02231-7

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