PAX3 Promotes Proliferation of Human Glioma Cells by WNT/β-Catenin Signaling Pathways
PAX3 Promotes Proliferation of Human Glioma Cells by WNT/β-Catenin Signaling Pathways
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DOI：
10.1007/s12031-019-01283-2
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发表时间：
2019-05-01
影响因子：
3.1
通讯作者：
Sun Caixing
中科院分区：
文献类型：
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作者：
Xia Liang;Zhao Dong;Sun Caixing
PAX 3（配对盒3）基因在胚胎发育、疾病和癌症形成中起着重要作用。我们的初步研究表明PAX 3基因在胶质瘤细胞中表达上调，这与预后不良有关。此外，PAX 3通过促进细胞增殖和侵袭以及抑制细胞凋亡，在胶质瘤中发挥致癌作用。然而，PAX 3作为癌基因在胶质瘤中发挥作用的具体分子机制仍不清楚。在本研究中，我们发现PAX 3过表达在高级别胶质瘤中观察到，并预测预后较差。PAX 3过表达与IDH 1突变和MGMT甲基化无显著相关性。此外，PAX 3的表达与β-连环蛋白的表达呈正相关。在U87胶质瘤细胞中，PAX 3与β-连环蛋白相互作用，如通过CO-IP证实的。此外，PAX 3过表达可促进细胞增殖和细胞周期进程，同时通过改变与Wnt信号通路相关的重要分子，包括β-catenin、Myc、VEGF、cyclinD 1、MMP 7和Wnt 1的表达来抑制细胞凋亡。同时也证实PAX 3与β-catenin通过负调控机制相互作用，促进U87胶质瘤细胞增殖和细胞周期进程，抑制细胞凋亡。我们的实验证明PAX 3在促进胶质瘤生长和发展中的作用，可能通过直接与β-catenin相互作用并调节Wnt信号通路。
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 beta-catenin. In U87 glioma cells, PAX3 interacted with beta-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 beta-catenin, Myc, VEGF, cyclinD1, MMP7, and Wnt1. In the meantime, it was also proved that PAX3 correlated to beta-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 beta-catenin and regulating the Wnt signaling pathway.