凝集素
癌变
巨噬细胞
癌症研究
脑膜瘤
转录组
肿瘤微环境
恶性脑膜瘤
川地163
恶性肿瘤
下调和上调
肿瘤坏死因子α
生物
医学
免疫学
细胞凋亡
癌症
病理
基因表达
遗传学
基因
体外
生物化学
肿瘤细胞
作者
Chao Ke,Boya Huang,Jian Xiang,Jinlian Liang,Guohui Wu,Minghui Qiu,Kai Chen,Lipeng Mao,Wen Li,Hanshuo Yang,Xushan Tang,Ye Tian,Guobing Chen,Oscar Junhong Luo,Hongyi Zhang
出处
期刊:Neuro-oncology
[Oxford University Press]
日期:2024-02-28
标识
DOI:10.1093/neuonc/noae034
摘要
Abstract Background Meningioma is the most common primary intracranial tumor with high frequency of postoperative recurrence, yet the biology of meningioma malignancy process is still obscure. Methods To identify potential therapeutic targets and tumor suppressors, we performed single-cell transcriptome analysis through meningioma malignancy, which included 18 samples spanning normal meninges, benign and high grade in situ tumors, and lung metastases, for extensive transcriptome characterization. Tumor suppressor candidate gene and molecular mechanism were functionally validated at animal model and cellular level. Results Comprehensive analysis and validation in mice and clinical cohorts indicated Clusterin (CLU) had suppressive function for meningioma tumorigenesis and malignancy by inducing mitochondria damage and triggering type I interferon pathway dependent on its secreted isoform, and the inhibition effect was enhanced by TNFα as TNFα also induced type I interferon pathway. The expression of CLU was upregulated by histone deacetylase inhibition. Meanwhile, both intra- and extra-cellular CLU overexpression enhanced macrophage polarization towards M1 phenotype and TNFα production, thus promoted tumor killing and phagocytosis. Conclusions CLU might be a key brake of meningioma malignance by synchronous modulating tumor cells and their microenvironment. Our work provides comprehensive insights into meningioma malignancy and a potential therapeutic strategy.
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