To identify biomarkers for glioma growth, invasion and progression, we used a candidate gene approach in mouse models with two complementary brain tumour phenotypes, developing either slow-growing, diffusely infiltrating gliomas or highly proliferative, non-invasive primitive neural tumours. In a microRNA screen we first identified microRNA-449a as most significantly differentially expressed between these two tumour types. miR-449a has a target dependent effect, inhibiting cell growth and migration by downregulation of CCND1 and suppressing neural phenotypes by inhibition of G protein coupled-receptor (GPR) 158. GPR158 promotes glioma stem cell differentiation and induces apoptosis and is highest expressed in the cerebral cortex and in oligodendrogliomas, lower in IDH mutant astrocytomas and lowest in the most malignant form of glioma, IDH wild-type glioblastoma. The correlation of GPR158 expression with molecular subtypes, patient survival and therapy response suggests a possible role of GPR158 as prognostic biomarker in human gliomas.

中文翻译：

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microRNA-449a 对 GPR158 的抑制可抑制神经胶质瘤干细胞/祖细胞的神经谱系，并与较高的神经胶质瘤级别相关。


为了确定神经胶质瘤生长、侵袭和进展的生物标志物，我们在具有两种互补脑肿瘤表型的小鼠模型中使用了候选基因方法，形成缓慢生长、弥漫浸润的神经胶质瘤或高度增殖、非侵袭性原始神经肿瘤。在 microRNA 筛选中，我们首先鉴定出 microRNA-449a 在这两种肿瘤类型之间表达差异最显着。 miR-449a 具有靶点依赖性效应，通过下调 CCND1 抑制细胞生长和迁移，并通过抑制 G 蛋白偶联受体 (GPR) 158 抑制神经表型。GPR158 促进胶质瘤干细胞分化并诱导细胞凋亡，在胶质瘤干细胞中表达最高。在大脑皮层和少突胶质细胞瘤中，IDH 突变型星形细胞瘤的含量较低，在最恶性的胶质瘤形式（IDH 野生型胶质母细胞瘤）中含量最低。 GPR158 表达与分子亚型、患者生存和治疗反应的相关性表明 GPR158 作为人类神经胶质瘤的预后生物标志物的可能作用。