BACKGROUND The primary features of malignant glioma include high rates of mortality and recurrence, uncontrollable invasiveness, strong angiogenesis, and widespread hypoxia. The hypoxic microenvironment is an important factor affecting the malignant progression of glioma. However, the molecular mechanisms underlying glioma adaption in hypoxic microenvironments are poorly understood. OBJECTIVE The work presented in this paper focuses on the role of WNK3 gene in glioma invasion under hypoxic conditions. Furthermore, we aim to explore its role in epithelial-to-mesenchymal transition (EMT). METHODS ShRNA targeting WNK3 transfection was used to knockdown the WNK3 expression in U87 cells. We used western blot analysis to detect the relative expression of proteins in U87 cells. The effect of WNK3 on cell migration was explored using a transwell assay in the U87 cell line. We also evaluated WNK3 expression levels in glioma samples by immunohistochemistry analysis. RESULTS WNK3 expression was significantly higher in high-grade (III and IV) gliomas than in low-grade (I and II) gliomas. WNK3 expression was up-regulated in U87 cells when cultured in a hypoxic environment in addition; WNK3 knockdown inhibited the invasion of U87 glioma cells by regulating the EMT, especially under hypoxic conditions. CONCLUSION These findings suggested that WNK3 plays an important role in the hypoxic microenvironment of glioma and might also be a candidate for therapeutic application in the treatment of glioma.

中文翻译：

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WNK3通过诱导上皮-间质转化促进缺氧条件下胶质瘤细胞系的侵袭性。

背景恶性神经胶质瘤的主要特征包括高死亡率和复发率、不可控制的侵袭性、强血管生成和广泛缺氧。低氧微环境是影响胶质瘤恶性进展的重要因素。然而，对低氧微环境中胶质瘤适应的分子机制知之甚少。目的本文介绍的工作重点是低氧条件下WNK3基因在胶质瘤侵袭中的作用。此外，我们旨在探索其在上皮间质转化 (EMT) 中的作用。方法 靶向WNK3转染的ShRNA用于敲低U87细胞中WNK3的表达。我们使用蛋白质印迹分析来检测 U87 细胞中蛋白质的相对表达。在 U87 细胞系中使用 transwell 测定探索了 WNK3 对细胞迁移的影响。我们还通过免疫组织化学分析评估了神经胶质瘤样本中的 WNK3 表达水平。结果 WNK3 在高级别（III 和 IV）胶质瘤中的表达明显高于低级别（I 和 II）胶质瘤。此外，在缺氧环境中培养时，U87 细胞中 WNK3 表达上调；WNK3 敲低通过调节 EMT 来抑制 U87 胶质瘤细胞的侵袭，尤其是在缺氧条件下。结论这些发现表明WNK3在胶质瘤缺氧微环境中发挥重要作用，也可能成为胶质瘤治疗应用的候选者。结果 WNK3 在高级别（III 和 IV）胶质瘤中的表达明显高于低级别（I 和 II）胶质瘤。此外，在缺氧环境中培养时，U87 细胞中 WNK3 表达上调；WNK3 敲低通过调节 EMT 来抑制 U87 胶质瘤细胞的侵袭，尤其是在缺氧条件下。结论这些发现表明WNK3在胶质瘤缺氧微环境中发挥重要作用，也可能成为胶质瘤治疗应用的候选者。结果 WNK3 在高级别（III 和 IV）胶质瘤中的表达明显高于低级别（I 和 II）胶质瘤。此外，在缺氧环境中培养时，U87 细胞中 WNK3 表达上调；WNK3 敲低通过调节 EMT 来抑制 U87 胶质瘤细胞的侵袭，尤其是在缺氧条件下。结论这些发现表明WNK3在胶质瘤缺氧微环境中发挥重要作用，也可能成为胶质瘤治疗应用的候选者。