EMX1 functions as a tumor inhibitor in spinal cord glioma through transcriptional suppression of WASF2 and inactivation of the Wnt/β-catenin axis.

Ziyin Han, Zufang Mou, Yulong Jing, Rong Jiang, Tao Sun

Brain and behavior 2022 Aug

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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. © 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.

Citation

Ziyin Han, Zufang Mou, Yulong Jing, Rong Jiang, Tao Sun. EMX1 functions as a tumor inhibitor in spinal cord glioma through transcriptional suppression of WASF2 and inactivation of the Wnt/β-catenin axis. Brain and behavior. 2022 Aug;12(8):e2684