Abstract：
The high expression of MEOX2 transcription factor is closely associated with poor overall survival in glioma. MEOX2 has recently been described as an interesting prognostic biomarker, especially for lower grade glioma. MEOX2 has never been studied in glioma stem-like cells (GSC), responsible for glioma recurrence. The aim of our study was to investigate the role of MEOX2 in GSC. Loss of function approach using siRNA was used to assess the impact of MEOX2 on GSC viability and stemness phenotype. MEOX2 was localized in the nucleus and its expression was heterogeneous between GSCs. MEOX2 expression depends on the methylation state of its promoter and is strongly associated with IDH mutations. MEOX2 is involved in cell proliferation and viability regulation through ERK/MAPK and PI3K/AKT pathways. MEOX2 loss of function correlated with GSC differentiation and acquisition of neuronal lineage characteristics. Besides, inhibition of MEOX2 is correlated with increased expression of CDH10 and decreased pFAK. In this study, we unraveled, for the first time, MEOX2 contribution to cell viability and proliferation through AKT/ERK pathway and its potential involvement in phenotype and adhesion properties of GSC.
摘要：
MEOX2转录因子的高表达与胶质瘤总体生存率低密切相关。MEOX2最近被描述为一个有趣的预后生物标志物，尤其是低级别的神经胶质瘤。MEOX2从未在神经胶质瘤干细胞样细胞（GSC）中进行过研究，负责胶质瘤复发。本研究旨在探讨MEOX2在GSC中的作用。使用siRNA的功能丧失方法用于评估MEOX2对GSC活力和干性表型的影响。MEOX2位于细胞核中，其表达在GSC之间是异质的。MEOX2表达取决于其启动子的甲基化状态，并且与IDH突变密切相关。MEOX2通过ERK/MAPK和PI3K/AKT途径参与细胞增殖和活力调节。MEOX2功能丧失与GSC分化和神经元谱系特征的获得相关。此外,MEOX2的抑制与CDH10的表达增加和pFAK的降低相关。在这项研究中,我们解开了，第一次,MEOX2通过AKT/ERK途径促进细胞活力和增殖，并可能参与GSC的表型和粘附特性。
