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微小RNA-130b通过靶向CYLD调节胶质瘤细胞的增殖、侵袭和凋亡。

miR-130b regulates the proliferation, invasion and apoptosis of glioma cells via targeting of CYLD.

作者信息

Xiao Zhi-Qiang, Yin Teng-Kun, Li Ya-Xing, Zhang Jian-He, Gu Jian-Jun

机构信息

Department of Neurosurgery, The First People's Hospital of Shangqiu, Shangqiu, Henan 476100, P.R. China.

Department of Neurosurgery, Fuzong Clinical College, Fujian Medical University, Fuzhou, Fujian 350025, P.R. China.

出版信息

Oncol Rep. 2017 Jul;38(1):167-174. doi: 10.3892/or.2017.5651. Epub 2017 May 19.

DOI:10.3892/or.2017.5651
PMID:28534976
Abstract

MicroRNAs are short non-coding RNAs that play important roles in gliomas. However, the role of miR-130b in glioma remains unclear. In the present study, miR-130b expression was upregulated in glioma tissues and cell lines. Kaplan-Meier analysis indicated that the upregulation of miR-130b expression correlated with poor prognoses in glioma patients. Multivariate analysis demonstrated that this upregulation and a high-grade classification were independent factors that both predicted poor outcomes for glioma patients. Dual-luciferase assays identified that the cylindromatosis (CYLD) gene is a direct target of miR-130b. Functional studies demonstrated that a miR-130b mimic significantly promoted the growth and invasion of glioma cells, while also inhibiting apoptosis via selective targeting of CYLD, which was enhanced by CYLD-targeted siRNA. In contrast, a miR‑130b inhibitor suppressed these biological behaviors, and this inhibition was reversed by CYLD-targeted siRNA. These data revealed that miR-130b could act as a novel potential diagnostic biomarker for glioma, while also demonstrating the importance of miR‑130b in the cell proliferation and progression of glioma, indicating that it may serve as a useful therapeutic target for glioma.

摘要

微小RNA是短链非编码RNA,在胶质瘤中发挥重要作用。然而,miR-130b在胶质瘤中的作用仍不清楚。在本研究中,miR-130b在胶质瘤组织和细胞系中表达上调。Kaplan-Meier分析表明,miR-130b表达上调与胶质瘤患者的不良预后相关。多变量分析表明,这种上调和高级别分类是预测胶质瘤患者不良结局的独立因素。双荧光素酶测定确定圆柱瘤蛋白(CYLD)基因是miR-130b的直接靶点。功能研究表明,miR-130b模拟物显著促进胶质瘤细胞的生长和侵袭,同时通过选择性靶向CYLD抑制细胞凋亡,而靶向CYLD的小干扰RNA可增强这种作用。相反,miR-130b抑制剂抑制了这些生物学行为,而靶向CYLD的小干扰RNA可逆转这种抑制作用。这些数据表明,miR-130b可作为胶质瘤一种新的潜在诊断生物标志物,同时也证明了miR-130b在胶质瘤细胞增殖和进展中的重要性,表明它可能是胶质瘤的一个有用治疗靶点。

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