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小胶质细胞表达的 MS4A6A 在胶质母细胞瘤发病中的作用。

Involvement of microglia-expressed MS4A6A in the onset of glioblastoma.

机构信息

School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China.

School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China.

出版信息

Eur J Neurosci. 2024 May;59(10):2836-2849. doi: 10.1111/ejn.16309. Epub 2024 Mar 15.

Abstract

Glioblastoma multiforme (GBM) represents the deadliest form of brain tumour, characterized by its low survival rate and grim prognosis. Cytokines released from glioma-associated microglia/macrophages are involved in establishing the tumour microenvironment, thereby crucially promoting GBM progression. MS4A6A polymorphism was confirmed to be associated with neurodegenerative and polymorphism disease pathobiology, but whether it participates in the regulation of GBM and the underlying mechanisms is still not elucidated. Here, we found that MS4A6A was significantly upregulated in GBM patient samples. The results from the single-cell RNA-sequencing (scRNA-seq) database and immunostaining demonstrated the specific expression of MS4A6A in microglial cells. In vitro, microglial overexpression of MS4A6A stimulated the proliferation and migration of glioblastoma cells. Moreover, high MS4A6A mRNA expression was related to poor prognosis in GBM patients. Our study highlights the potential of MS4A6A as a promising biomarker for GBM, which may provide novel strategies for its prevention, diagnosis and treatment.

摘要

多形性胶质母细胞瘤(GBM)是最致命的脑肿瘤形式,其特点是存活率低,预后不良。胶质瘤相关小胶质细胞/巨噬细胞释放的细胞因子参与肿瘤微环境的建立,从而严重促进 GBM 的进展。MS4A6A 多态性被证实与神经退行性和多态性疾病的病理生物学有关,但它是否参与 GBM 的调节及其潜在机制仍不清楚。在这里,我们发现 MS4A6A 在 GBM 患者样本中显著上调。单细胞 RNA 测序(scRNA-seq)数据库和免疫染色的结果表明 MS4A6A 特异性表达于小胶质细胞中。在体外,小胶质细胞中 MS4A6A 的过表达刺激了神经胶质瘤细胞的增殖和迁移。此外,MS4A6A 的高 mRNA 表达与 GBM 患者的不良预后相关。我们的研究强调了 MS4A6A 作为 GBM 有前途的生物标志物的潜力,这可能为其预防、诊断和治疗提供新的策略。

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