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.
Glioma PAX3 Wnt β-Catenin Oncogene
Isocitrate dehydrogenase 1
Glial fibrillary acidic protein
World Health Organization
Karnofsky Performance Scale
N-terminal transcription inhibitory domain
Terminal trans-activation domain
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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.
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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All authors declare that they have no conflict of interests.
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