Department of Neurosurgery, Zhejiang Cancer Hospital, 1 Ban Shan east road, Hangzhou, 310022, Zhejiang Province, China.
Department of Neurosurgery, Zhejiang Hospital, 12 Lingyin road, Hangzhou, 310013, Zhejiang Province, China.
J Mol Neurosci. 2019 May;68(1):66-77. doi: 10.1007/s12031-019-01283-2. Epub 2019 Mar 2.
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.
PAX3（配对盒 3）基因在胚胎发育、疾病和癌症形成中发挥重要作用。我们的初步研究表明，PAX3 基因在神经胶质瘤细胞中上调，与预后不良有关。此外，PAX3 通过促进细胞增殖和侵袭，抑制细胞凋亡，在神经胶质瘤中发挥致癌作用。然而，PAX3 作为神经胶质瘤致癌基因的具体分子机制尚不清楚。在本研究中，我们发现 PAX3 在高级别神经胶质瘤中过表达，且预测预后不良。PAX3 过表达与 IDH1 突变和 MGMT 甲基化无显著相关性。此外，PAX3 的表达与 β-catenin 的表达呈正相关。在 U87 神经胶质瘤细胞中，PAX3 与 β-catenin 相互作用，这一点通过 CO-IP 得到了证实。此外，PAX3 过表达通过改变与 Wnt 信号通路相关的重要分子的表达，促进细胞增殖和细胞周期进程，同时抑制细胞凋亡，这些分子包括 β-catenin、Myc、VEGF、cyclinD1、MMP7 和 Wnt1。同时，也证明了 PAX3 通过与 β-catenin 的负反馈调节机制，促进 U87 神经胶质瘤细胞的增殖、细胞周期进程，并抑制细胞凋亡。我们的实验证明了 PAX3 在促进神经胶质瘤生长和发展中的作用，可能是通过与 β-catenin 直接相互作用并调节 Wnt 信号通路来实现的。
