Glioblastoma (GBM) is the most common, malignant, and aggressive form of glial cell cancer with unfavorable clinical outcomes. It is believed that a better understanding of the mechanisms of gene deregulation may lead to novel therapeutic approaches for this yet incurable cancer. Mediator complex is a crucial component of enhancer-based gene expression and works as a transcriptional co-activator. Many of the mediator complex subunits are found to be deregulated/mutated in various malignancies; however, their status and role in GBM remains little studied. We report that MED30, a core subunit of the head module, is overexpressed in GBM tissues and cell lines. MED30 was found to be induced by conditions present in the tumor microenvironment such as hypoxia, serum, and glucose deprivation. MED30 harbors hypoxia response elements (HREs) and p53 binding site in its promoter and is induced in a HIF1α and p53 dependent manner. Further, MED30 levels also significantly positively correlated with p53 and HIF1α levels in GBM tissues. Using both MED30 overexpression and knockdown approach, we show that MED30 promotes cell proliferation while reduces the migration capabilities in GBM cell lines. Notably, MED30 was also found to confer sensitivity to chemodrug, temozolomide, in GBM cells and modulate the level of p53 in vitro. Overall, this is the first report showing MED30 overexpression in GBM and its involvement in GBM pathogenesis suggesting its diagnostic and therapeutic potential urging the need for further systematic exploration of MED30 interactome and target networks.

胶质母细胞瘤 (GBM) 是最常见、恶性和侵袭性的胶质细胞癌形式，具有不利的临床结果。人们相信，更好地理解基因失调的机制可能会为这种尚未治愈的癌症带来新的治疗方法。介体复合物是基于增强子的基因表达的重要组成部分，可作为转录共激活因子。发现许多介体复合物亚基在各种恶性肿瘤中失调/突变；然而，它们在 GBM 中的地位和作用仍然很少被研究。我们报告 MED30，头部模块的核心亚基，在 GBM 组织和细胞系中过度表达。发现 MED30 是由肿瘤微环境中存在的条件诱导的，例如缺氧、血清和葡萄糖剥夺。MED30 在其启动子中含有缺氧反应元件 (HRE) 和 p53 结合位点，并以 HIF1α 和 p53 依赖性方式诱导。此外，MED30 水平也与 GBM 组织中的 p53 和 HIF1α 水平显着正相关。使用 MED30 过表达和敲低方法，我们表明 MED30 促进细胞增殖，同时降低 GBM 细胞系的迁移能力。值得注意的是，MED30 还被发现赋予 GBM 细胞对化学药物替莫唑胺的敏感性，并在体外调节 p53 的水平。总体而言，这是第一份显示 MED30 在 GBM 中过表达及其参与 GBM 发病机制的报告，表明其诊断和治疗潜力促使需要进一步系统探索 MED30 相互作用组和靶网络。