胶质1
基因敲除
癌症研究
转录因子
音猬因子
肿瘤坏死因子α
炎症
生物
癌基因
刺猬信号通路
信号转导
免疫学
细胞生物学
细胞
基因
细胞周期
遗传学
作者
Jingyi Zhao,Yongqiang Yang,Yuanyuan Pan,Pengcheng Zhou,Juan Wang,Yingjuan Zheng,Xiangxian Zhang,Suna Zhai,Xiqian Zhang,Liming Li,Daoke Yang
标识
DOI:10.1021/acschemneuro.3c00031
摘要
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.
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