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miRNA-378 通过靶向 IRG1 作为人神经胶质瘤的预后标志物并抑制细胞迁移、侵袭和上皮-间充质转化。

MicroRNA-378 acts as a prognosis marker and inhibits cell migration, invasion and epithelial-mesenchymal transition in human glioma by targeting IRG1.

机构信息

Department of Neurosurgery, Yantaishan Hospital, Yantai, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Jun;22(12):3837-3846. doi: 10.26355/eurrev_201806_15268.

DOI:10.26355/eurrev_201806_15268
PMID:29949160
Abstract

OBJECTIVE

Glioma is one common intracranial malignancy. Recently, there has been a large volume of published studies describing the functions of microRNAs as potential diagnostic markers for glioma. Data from several sources revealed that miR-378 played crucial roles in multiple tumors. However, much uncertainty still exists about the functions and underlying mechanism of miR-378. The purpose of the present work was to evaluate the potential effect of miR-378 and verify its influence on the function of IRG1 in glioma.

PATIENTS AND METHODS

The miR-378 expression was examined in 52 pairs of glioma tissues using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Transwell assays were conducted to detect the capability of glioma cell migration and invasion with different transfections. Luciferase reporter was used to confirm whether miR-378 could regulate immune responsive gene 1 (IRG1). Western blot was used to measure the expressions of EMT-related markers.

RESULTS

miR 378 expressions were notably reduced in glioma cells and tissues in comparison with controls. The declined miR-378 expressions were correlated with the poor OS and worse clinicopathological parameters of glioma patients. Overexpression of miR-378 repressed glioma cell epithelial-mesenchymal transition (EMT) and metastasis as well as the tumor growth rate and tumor size of glioma mice. Additionally, IRG1 was markedly up-regulated in glioma and was confirmed as a direct target for miR 378 in glioma.

CONCLUSIONS

We showed that the suppressive role of miR-378 in glioma, which was regulated by IRG1, suggested that the miR-378/IRG1 axis may be an effective target for glioma treatment.

摘要

目的

脑胶质瘤是一种常见的颅内恶性肿瘤。最近,有大量发表的研究描述了 microRNAs 作为脑胶质瘤潜在诊断标志物的功能。来自多个来源的数据表明,miR-378 在多种肿瘤中发挥着关键作用。然而,miR-378 的功能和潜在机制仍存在很大的不确定性。本研究旨在评估 miR-378 的潜在作用,并验证其对脑胶质瘤中免疫反应基因 1(IRG1)功能的影响。

患者和方法

采用实时定量聚合酶链反应(qRT-PCR)检测 52 对脑胶质瘤组织中 miR-378 的表达。采用 Transwell 实验检测不同转染后脑胶质瘤细胞迁移和侵袭的能力。荧光素酶报告实验用于证实 miR-378 是否可以调节免疫反应基因 1(IRG1)。Western blot 用于测量 EMT 相关标记物的表达。

结果

与对照组相比,脑胶质瘤细胞和组织中的 miR 378 表达明显降低。下调的 miR-378 表达与脑胶质瘤患者的不良 OS 和更差的临床病理参数相关。过表达 miR-378 抑制了脑胶质瘤细胞上皮-间充质转化(EMT)和转移,以及脑胶质瘤小鼠的肿瘤生长速度和肿瘤大小。此外,IRG1 在脑胶质瘤中明显上调,并被证实为 miR 378 在脑胶质瘤中的直接靶标。

结论

我们表明,miR-378 在脑胶质瘤中的抑制作用是由 IRG1 调节的,这表明 miR-378/IRG1 轴可能是脑胶质瘤治疗的有效靶点。

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