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β4GalT1 在体内和体外脑胶质瘤中的作用和机制研究。

Study on the role and mechanism of β4GalT1 both in vivo and in vitro glioma.

机构信息

Department of Laboratory Medicine, Deyang People's Hospital, Deyang, P.R. China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Apr;24(8):4368-4381. doi: 10.26355/eurrev_202004_21018.

Abstract

OBJECTIVE

To discuss the role and mechanism of β4GalT1 both in vivo and in vitro glioma, observe whether pathophysiological processes of glioma can be improved after β4GalT1 is knocked down, and study whether β4GalT1 plays a role in malignant biological processes of glioma by regulating the apoptosis and immune processes.

PATIENTS AND METHODS

Firstly, the distribution difference of β4GalT1 in tumor tissues and normal tissues was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) tumor analysis system to deduce the possible role of β4GalT1 in glioma. Secondly, whether the malignant degree of glioma was related to the expression of β4GalT1 and its immunity using human tumor tissues and blood lymphocyte subsets was analyzed. Thirdly, interfere lentivirus vector with β4GalT1 and knockdown β4GalT1 was analyzed to observe whether the malignant degree of glioma has changed. Fourthly, interfere lentivirus vector with recombinant β4GalT protein and β4GalT1 was analyzed to verify the effect of β4GalT in vitro test. Fifth, interfere lentivirus vector with recombinant β4GalT protein and β4GalT1 was analyzed to verify effect of β4GalT in vivo test. Finally, we discuss whether β4GalT is involved in the biological process of glioma through inflammatory reaction.

RESULTS

In the GEPIA tumor analysis system, the expression in tumor was significantly higher than that in normal tissues. The expression of β4GalT1 in glioma tissues was higher than that in normal tissues, and the higher the malignancy of the tumor, the higher the expression of β4GalT1 in the glioma tissues, and the lower the immune level was. The expression of IDH1, MGMT, and ki-67 was reduced, and the survival rate of the mice with glioma was improved after β4GalT1 was knocked down. In vitro tests, the activity of tumor cells and their reproductive ability can be reduced after β4GalT1 was knocked down, the immune level of the body can be improved, and the level of tissue apoptosis can be reduced. After recombinant β4GalT1 was given alone, the result was opposite to that of β4GalT1 knocked down group. In vivo tests, gross tumor volume can be reduced after β4GalT1 was knocked down, the immune level of the body can be improved, and the level of tissue apoptosis can be reduced. After recombinant β4GalT1 was given alone, the result was opposite to that of β4GalT1 knocked down group. After knocking down β4GalT1, the expression of inflammatory factors can be reduced both in vivo and in vitro, and the inflammatory microenvironment of tumors can be improved. After recombinant β4GalT1 was given alone, the result was opposite to that of β4GalT1 knocked down group.

CONCLUSIONS

The level of β4GalT1 expression in tumor tissues was increased. The malignant degree of glioma is related to the expression of β4GalT1 and its immunity. The level of tumor marker can be decreased, and the survival rate of glioma model mice can be increased after β4GalT1 is knocked down. Apoptosis and immune injury caused by tumor can be improved and gross tumor volume can be deduced after β4GalT1 is knocked down. During the development of glioma, β4GalT1 may play a malignant biological role through inflammatory response.

摘要

目的

探讨β4GalT1 在体内和体外胶质瘤中的作用和机制,观察敲低β4GalT1 后是否能改善胶质瘤的病理生理过程,并通过调节细胞凋亡和免疫过程研究β4GalT1 是否在胶质瘤的恶性生物学过程中发挥作用。

患者和方法

首先,通过基因表达谱交互分析(GEPIA)肿瘤分析系统分析β4GalT1 在肿瘤组织和正常组织中的分布差异,推断β4GalT1 可能在胶质瘤中的作用。其次,用人肿瘤组织和血淋巴细胞亚群分析β4GalT1 及其免疫与胶质瘤恶性程度的关系。第三,用干扰慢病毒载体敲低β4GalT1,观察其对胶质瘤恶性程度的影响。第四,用重组β4GalT 蛋白和β4GalT1 干扰慢病毒载体验证β4GalT 的体外试验效果。第五,用重组β4GalT 蛋白和β4GalT1 干扰慢病毒载体验证β4GalT 的体内试验效果。最后,我们通过炎症反应探讨β4GalT 是否参与胶质瘤的生物学过程。

结果

在 GEPIA 肿瘤分析系统中,肿瘤中的表达明显高于正常组织。胶质瘤组织中β4GalT1 的表达高于正常组织,肿瘤恶性程度越高,胶质瘤组织中β4GalT1 的表达越高,免疫水平越低。β4GalT1 被敲低后 IDH1、MGMT 和 ki-67 的表达减少,胶质瘤小鼠的存活率提高。体外试验中,β4GalT1 被敲低后肿瘤细胞活性及其生殖能力降低,机体免疫水平提高,组织凋亡水平降低。单独给予重组β4GalT1 后,结果与敲低β4GalT1 组相反。体内试验中,β4GalT1 被敲低后肿瘤体积减小,机体免疫水平提高,组织凋亡水平降低。单独给予重组β4GalT1 后,结果与敲低β4GalT1 组相反。β4GalT1 被敲低后,无论是在体内还是体外,炎症因子的表达都减少,肿瘤的炎症微环境得到改善。单独给予重组β4GalT1 后,结果与敲低β4GalT1 组相反。

结论

肿瘤组织中β4GalT1 的表达水平升高。胶质瘤的恶性程度与β4GalT1 的表达及其免疫有关。敲低β4GalT1 后肿瘤标志物水平降低,胶质瘤模型小鼠存活率提高。敲低β4GalT1 后可改善肿瘤引起的细胞凋亡和免疫损伤,减少肿瘤体积。在胶质瘤的发展过程中,β4GalT1 可能通过炎症反应发挥恶性生物学作用。

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