Abstract：
Adamantinomatous craniopharyngioma (ACP) is a neuroendocrine tumor whose pathogenesis remains unclear. This study investigated the role of glioma-associated oncogene family zinc finger 1 (GLI1), a transcription factor in the sonic hedgehog (SHH) signaling pathway, in ACP. We discovered that GLI1 regulates the expression of IL-6, thereby triggering inflammatory responses in ACP and influencing the tumor\'s progression. Analyzing the Gene Expression Omnibus (GEO) database chip GSE68015, we found that GLI1 is overexpressed in ACP, correlating positively with the spite of ACP and inflammation markers. Knockdown of GLI1 significantly inhibited the levels of tumor necrosis factor α, interleukin-6 (IL-6), and IL-1β in ACP cells, as well as cell proliferation and migration. We further identified a binding site between GLI1 and the promoter region of IL-6, demonstrating that GLI1 can enhance the expression of IL-6. These findings were verified in vivo, where activation of the SHH pathway significantly promoted GLI1 and IL-6 expressions in nude mice, inducing inflammation and tumor growth. Conversely, GLI1 knockdown markedly suppressed these processes. Our study uncovers a potential molecular mechanism for the occurrence of inflammatory responses and tumor progression in ACP.
摘要：
Adamantinomatic颅咽管瘤（ACP）是一种神经内分泌肿瘤，其发病机制尚不清楚。这项研究调查了神经胶质瘤相关癌基因家族锌指1（GLI1）的作用，声波刺猬（SHH）信号通路中的转录因子，在ACP。我们发现GLI1调节IL-6的表达，从而在ACP中引发炎症反应并影响肿瘤的进展。分析基因表达综合（GEO）数据库芯片GSE68015，我们发现GLI1在ACP中过度表达，尽管ACP和炎症标志物呈正相关。GLI1敲低可显著抑制肿瘤坏死因子α水平,白细胞介素-6（IL-6），ACP细胞中的IL-1β,以及细胞增殖和迁移。我们进一步鉴定了GLI1与IL-6启动子区之间的结合位点,证明GLI1可以增强IL-6的表达。这些发现在体内得到了验证，其中SHH途径的激活显着促进裸鼠GLI1和IL-6的表达，诱导炎症和肿瘤生长。相反，GLI1敲低显著抑制了这些过程。我们的研究揭示了ACP中炎症反应发生和肿瘤进展的潜在分子机制。
