Department of Traumatic Orthopedics, Yantaishan Hospital of Yantai, Yantai, Shandong, P.R. China.
Administration Department of Nosocomial Infection, Yantaishan Hospital of Yantai, Yantai, Shandong, P.R. China.
Brain Behav. 2022 Aug;12(8):e2684. doi: 10.1002/brb3.2684. Epub 2022 Jul 18.
Gliomas are the most frequent and aggressive cancers in the central nervous system, and spinal cord glioma (SCG) is a rare class of the gliomas. Empty spiracles homobox genes (EMXs) have shown potential tumor suppressing roles in glioma, but the biological function of EMX1 in SCG is unclear.
The EMX1 expression in clinical tissues of patients with SCG was examined. SCG cells were extracted from the tissues, and altered expression of EMX1 was then introduced to examine the role of EMX1 in cell growth and invasiveness in vitro. Xenograft tumors were induced in nude mice for in vivo validation. The targets of EXM1 were predicted via bioinformatic analysis and validated by luciferase and ChIP-qPCR assays. Rescue experiments were conducted to validate the involvements of the downstream molecules.
EMX1 was poorly expressed in glioma, which was linked to decreased survival rate of patients according to the bioinformatics prediction. In clinical tissues, EMX1 was poorly expressed in SCG, especially in the high-grade tissues. EMX1 upregulation significantly suppressed growth and metastasis of SCG cells in vitro and in vivo. EMX1 bound to the promoter of WASP family member 2 (WASF2) to suppress its transcription. Restoration of WASF2 blocked the tumor-suppressing effect of EMX1. EMX1 suppressed Wnt/β-catenin signaling activity by inhibiting WASF2. Coronaridine, a Wnt/β-catenin-specific antagonist, blocked SCG cell growth and metastasis induced by WASF2.
This study elucidates that EMX1 functions as a tumor inhibitor in SCG by suppressing WASF2-dependent activation of the Wnt/β-catenin axis.
神经胶质瘤是中枢神经系统中最常见和最具侵袭性的癌症，脊髓神经胶质瘤（SCG）是神经胶质瘤的一种罕见类型。空泡螺旋框同源盒基因（EMXs）在神经胶质瘤中显示出潜在的肿瘤抑制作用，但 EMX1 在 SCG 中的生物学功能尚不清楚。
检测了 EMX1 在 SCG 患者临床组织中的表达。从组织中提取 SCG 细胞，然后改变 EMX1 的表达，以体外研究 EMX1 在细胞生长和侵袭中的作用。在裸鼠中诱导异种移植肿瘤进行体内验证。通过生物信息学分析预测 EXM1 的靶标，并通过荧光素酶和 ChIP-qPCR 检测进行验证。进行挽救实验以验证下游分子的参与。
根据生物信息学预测，EMX1 在神经胶质瘤中表达较差，与患者生存率降低有关。在临床组织中，SCG 中的 EMX1 表达较差，特别是在高级别组织中。EMX1 的上调显著抑制了 SCG 细胞在体外和体内的生长和转移。EMX1 与 WASP 家族成员 2（WASF2）的启动子结合，抑制其转录。WASF2 的恢复阻断了 EMX1 的肿瘤抑制作用。EMX1 通过抑制 WASF2 抑制 Wnt/β-catenin 信号活性。冠状菌素，一种 Wnt/β-catenin 特异性拮抗剂，阻断了 WASF2 诱导的 SCG 细胞生长和转移。
本研究表明，EMX1 通过抑制 WASF2 依赖性激活 Wnt/β-catenin 轴，在 SCG 中发挥肿瘤抑制作用。
