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GINS2 的缺失抑制了人脑胶质瘤细胞的增殖和肿瘤生成。

Loss of GINS2 inhibits cell proliferation and tumorigenesis in human gliomas.

机构信息

Department of Neurosurgery, The Fifth Affiliated Hospital, South Medical University, Guangzhou, China.

Clinical Laboratory Department, Nanfang Hospital, Southern Medical University, Guangzhou, China.

出版信息

CNS Neurosci Ther. 2019 Feb;25(2):273-287. doi: 10.1111/cns.13064. Epub 2018 Oct 18.

Abstract

AIMS

In this study, we examined the expression of GINS2 in glioma and determined its role in glioma development.

METHODS

The protein expression of GINS2 was assessed in 120 human glioma samples via immunohistochemistry. Then, we suppressed the expression of GINS2 in glioma cell strains U87 and U251 using a short hairpin RNA lentiviral vector. In addition, RNA sequencing and bioinformatics analysis were performed on glioma cells before and after GINS2 knockdown. Subsequent co-immunoprecipitation and western blot experiments indicated possible downstream regulatory molecules.

RESULTS

The present results showed that GINS2 can accelerate the growth of glioma cells, whereas the suppression of GINS2 expression decreased the proliferation and tumorigenicity of glioma cells. Mechanism research experiments proved that GINS2 can block the cell cycle by regulating certain downstream molecules, such as MCM2, ATM, and CHEK2.

CONCLUSION

GINS2 is closely related to the occurrence and development of glioma, and is likely to become a prognostic marker for glioma patients, as well as a potential therapeutic target in the treatment of glioma.

摘要

目的

本研究检测了 GINS2 在神经胶质瘤中的表达,并确定其在神经胶质瘤发生发展中的作用。

方法

通过免疫组织化学方法检测 120 例人神经胶质瘤样本中 GINS2 的蛋白表达。然后,我们使用短发夹 RNA 慢病毒载体抑制神经胶质瘤细胞株 U87 和 U251 中 GINS2 的表达。此外,在敲低 GINS2 前后对神经胶质瘤细胞进行 RNA 测序和生物信息学分析。随后的共免疫沉淀和 Western blot 实验表明可能存在下游调节分子。

结果

本研究结果表明,GINS2 可以促进神经胶质瘤细胞的生长,而抑制 GINS2 表达则降低了神经胶质瘤细胞的增殖和致瘤性。机制研究实验证明,GINS2 可以通过调节某些下游分子,如 MCM2、ATM 和 CHEK2,来阻断细胞周期。

结论

GINS2 与神经胶质瘤的发生发展密切相关,可能成为神经胶质瘤患者的预后标志物,以及神经胶质瘤治疗的潜在治疗靶点。

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