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ADAMTS8 抑制体外和体内脑胶质瘤的发展。

ADAMTS8 inhibits glioma development in vitro and in vivo.

机构信息

Neurosurgical Department, Tianjin First Central Hospital, Nankai District, Tianjin, China.

出版信息

Folia Neuropathol. 2023;61(2):144-152. doi: 10.5114/fn.2023.129380.

DOI:10.5114/fn.2023.129380
PMID:37587889
Abstract

INTRODUCTION

In recent years, novel RNAs have been revealed to be regulators in glioma. ADAMTS8 has been reported to be reduced in brain tumours. In this study, we aimed to explore the role of ADAMTS8 in glioma.

MATERIAL AND METHODS

Online bioinformatic tools, Gepia and Chinese Glioma Genome Atlas database (CGGA) were used to analyse the differential expression of ADAMTS8, overall survival and disease-free survival rates and the correlations between ADAMTS8 and matrix metallopeptidases (MMP2 and MMP9) in glioma. RT-qPCR and western blot experiments were performed to measure the mRNA and protein expression. ADAMTS8 expression was regulated in cells through transfection. Thereafter, the effect of ADAMTS8 on cells was investigated through the cell viability, apoptosis and transwell experiments. The epithelial-mesenchymal transition (EMT)-related proteins and also MMP2 and MMP9 were examined. The subcutaneous tumour model was established to validate the suppressive role of ADAMTS8 in tumour growth.

RESULTS

ADAMTS8 expression was reduced in glioma tissues and cells. Higher expression of ADAMTS8 was correlated with higher survival rates. ADAMTS8 was correlated with MMP2 and MMP9 in glioma tissues. In glioma cells, overexpression of ADAMTS8 could inhibit the viability, invasion, migration and EMT, and MMP2 and MMP9, but promote the apoptosis of cells. The upregulation of ADAMTS8 could inhibit the tumour growth in vivo.

CONCLUSIONS

ADAMTS8 was inhibited in glioma and the higher expression of ADAMTS8 might be related to better prognosis among glioma patients. Overexpression of ADAMTS8 inhibited the development of glioma in vitro and in vivo.

摘要

简介

近年来,新的 RNA 被发现是神经胶质瘤的调控因子。已有研究报道,ADAMTS8 在脑肿瘤中表达降低。本研究旨在探讨 ADAMTS8 在神经胶质瘤中的作用。

材料和方法

利用在线生物信息学工具 Gepia 和中国脑胶质瘤基因组图谱数据库(CGGA)分析 ADAMTS8 的差异表达、总生存率和无病生存率,以及 ADAMTS8 与基质金属蛋白酶(MMP2 和 MMP9)在神经胶质瘤中的相关性。通过 RT-qPCR 和 Western blot 实验检测 ADAMTS8 的 mRNA 和蛋白表达。通过转染调节细胞中的 ADAMTS8 表达。然后通过细胞活力、细胞凋亡和 Transwell 实验研究 ADAMTS8 对细胞的影响。检测上皮-间充质转化(EMT)相关蛋白以及 MMP2 和 MMP9。建立皮下肿瘤模型验证 ADAMTS8 在肿瘤生长中的抑制作用。

结果

ADAMTS8 在神经胶质瘤组织和细胞中表达降低。ADAMTS8 表达水平较高与生存率较高相关。ADAMTS8 与神经胶质瘤组织中的 MMP2 和 MMP9 相关。在神经胶质瘤细胞中,过表达 ADAMTS8 可抑制细胞活力、侵袭、迁移和 EMT,以及 MMP2 和 MMP9,但促进细胞凋亡。ADAMTS8 的上调可抑制体内肿瘤生长。

结论

ADAMTS8 在神经胶质瘤中受到抑制,ADAMTS8 表达水平较高可能与神经胶质瘤患者的预后较好相关。ADAMTS8 的过表达可抑制神经胶质瘤在体外和体内的发展。

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