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PAX3 Promotes Proliferation of Human Glioma Cells by WNT/β-Catenin Signaling Pathways

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Abstract

The PAX3 (paired box 3) gene plays an important role in embryonic development, diseases, and cancer formation. Our preliminary studies have shown that PAX3 gene is upregulated in glioma cells, which is associated with a worse prognosis. Moreover, PAX3, by facilitating cell proliferation and invasion and inhibiting cell apoptosis, plays an oncogenic role in glioma. However, the specific molecular mechanism of PAX3 acting as an oncogene in glioma remains unclarified. In the present study, we have found that PAX3 overexpression was observed in high grade glioma and predicted a worse prognosis. PAX3 overexpression did not correlate significantly to IDH1 mutation and MGMT methylation. Moreover, the expression of PAX3 was positively correlated with that of β-catenin. In U87 glioma cells, PAX3 interacted with β-catenin, as was confirmed by CO-IP. Besides, PAX3 overexpression promoted cell proliferation and cell cycle progression, while it inhibited cell apoptosis by altering the expressions of important molecules associated with the Wnt signaling pathway, including β-catenin, Myc, VEGF, cyclinD1, MMP7, and Wnt1. In the meantime, it was also proved that PAX3 correlated to β-catenin through a negative regulatory mechanism with respect to the promotion of U87 glioma cell proliferation and cell cycle progression and inhibition of the cell apoptosis. Our experiment demonstrated the role of PAX3 in promoting glioma growth and development, possibly by interacting directly with β-catenin and regulating the Wnt signaling pathway.

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Abbreviations

PAX:

Paired box

CO-IP:

Co-immunoprecipitation

FCM:

Flow cytometry

IDH1:

Isocitrate dehydrogenase 1

MGMT:

O6-Methylguanine-DNA transferase

GFAP:

Glial fibrillary acidic protein

WHO:

World Health Organization

KPS:

Karnofsky Performance Scale

PD:

Paired domain

OCM:

Octapeptide motif

HD:

Home domain

ID:

N-terminal transcription inhibitory domain

TADC:

Terminal trans-activation domain

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Funding

The present study was supported by the National Natural Science Foundation of China (Grant No. 81502147), Zhejiang Medical Science and Technology Project (2017194140, 2018KY291, 2018248244), Natural Science Foundation of Jiangsu Province (BK20161318), and the third term “new medical talents of Zhejiang province” project.

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Author notes

  1. Xia Liang and Zhao Dong contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Zhejiang Cancer Hospital, 1 Ban Shan east road, Hangzhou, 310022, Zhejiang Province, China

    Xia Liang, Wu Bin, Zhang Shuyuan, Li Liwen, Jin Kai & Sun Caixing

  2. Department of Neurosurgery, Zhejiang Hospital, 12 Lingyin road, Hangzhou, 310013, Zhejiang Province, China

    Zhao Dong

  3. Department of Neurosurgery, Yancheng First Peoples’ Hospital, Yancheng, 224001, Jiangsu Province, China

    Nie Dekang

  4. Department of Head and Neck Surgery, Zhejiang Cancer Hospital, 1 Ban Shan east road, Hangzhou, 310022, Zhejiang Province, China

    Zhu Xuhang

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  1. Xia Liang
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  2. Zhao Dong
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  3. Wu Bin
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  7. Li Liwen
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  8. Jin Kai
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  9. Sun Caixing
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Contributions

SCX and XL conceived the project and participated in the study design, supervision of laboratory processes analysis, and interpretation of the results. XL conceived the writing of the manuscript. ZD and XL participated in the study design and drafting the manuscript. ZXH, NDK, and XL helped in vitro experiments and data analysis. ZD participated in the data interpretation and provided the critical review in the manuscript preparation. All authors read and approved the final manuscript.

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Correspondence to Sun Caixing.

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Liang, X., Dong, Z., Bin, W. et al. PAX3 Promotes Proliferation of Human Glioma Cells by WNT/β-Catenin Signaling Pathways. J Mol Neurosci 68, 66–77 (2019). https://doi.org/10.1007/s12031-019-01283-2

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