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MicroRNA-940 inhibits glioma cells proliferation and cell cycle progression by targeting CKS1

机译:MicroRNA-940通过靶向CKS1抑制神经胶质瘤细胞增殖和细胞周期进程

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摘要

Glioblastoma (GBM) is the most frequently occurred malignant human tumor that arise in brain with a poor prognosis. microRNAs (miRNAs) are vital small molecules during GBM initiation and progression. However, the expression of miR-940 and its potential function in GBM remain poor. Our study demonstrated that miR-940 was dramatically decreased in GBM cells and glioma tissues. Introduction of miR-940 significantly repressed proliferative ability of GBM cells. Notably, treatment of miR-940 dramatically suppressed tumor growth in an animal model, accompanied by decreased Ki67 expression. Functional experiments showed CKS1 as a target of miR-940, knockdown of CKS1 significantly induced the cell cycle arrest and restrained GBM cells proliferation, consistent with miR-940 treatment. Furthermore, reintroduction of CKS1 into glioma cells effectively rescued the tumor suppressive effect of miR-940. Correlation analysis indicated that miR-940 expression was inversely related to CKS1 mRNA levels in NBTs and gliomas. Together, miR-940/CKS1 signaling may be required for GBM progression and provide a new insight in diagnosis and prognosis of GBM patients.
机译:胶质母细胞瘤(GBM)是最常见的恶性人类肿瘤,发生于脑部,预后较差。 microRNA(miRNA)是GBM启动和发展过程中至关重要的小分子。但是,miR-940的表达及其在GBM中的潜在功能仍然很差。我们的研究表明,GBM细胞和神经胶质瘤组织中的miR-940显着降低。 miR-940的引入显着抑制了GBM细胞的增殖能力。值得注意的是,在动物模型中,miR-940的治疗显着抑制了肿瘤的生长,并伴有Ki67表达降低。功能实验表明CKS1是miR-940的靶标,CKS1的敲低显着诱导了细胞周期停滞并抑制了GBM细胞的增殖,与miR-940处理一致。此外,将CKS1重新引入神经胶质瘤细胞中有效地拯救了miR-940的肿瘤抑制作用。相关分析表明,miR-940的表达与NBTs和神经胶质瘤中CKS1 mRNA水平成反比。在一起,GBR进展可能需要miR-940 / CKS1信号传导,并为GBM患者的诊断和预后提供新的见解。

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