4.6 Article

Transcription Factor GLI1 Induces IL-6-Mediated Inflammatory Response and Facilitates the Progression of Adamantinomatous Craniopharyngioma

Journal

ACS CHEMICAL NEUROSCIENCE
Volume 14, Issue 18, Pages 3347-3356

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.3c00031

Keywords

glioma-associated oncogene family zinc finger 1; interleukin-6; adamantinomatous craniopharyngioma; tumor inflammation; sonic hedgehog pathway

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This study investigates the role of the transcription factor glioma-associated oncogene family zinc finger 1 (GLI1) in the sonic hedgehog signaling pathway in adamantinomatous craniopharyngioma (ACP). The study reveals that GLI1 regulates the expression of IL-6, triggering inflammatory responses and influencing tumor progression in ACP.
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 alpha, interleukin-6 (IL-6), and IL-1 beta 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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