真核起始因子 4A-3 通过 Notch1 依赖性途径促进胶质母细胞瘤的生长和侵袭。

Eukaryotic initiation factor 4 A-3 promotes glioblastoma growth and invasion through the Notch1-dependent pathway.

机构信息

Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, 530022, Guangxi, China.

Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, Guangxi, China.

出版信息

BMC Cancer. 2023 Jun 15;23(1):550. doi: 10.1186/s12885-023-10946-8.

DOI:10.1186/s12885-023-10946-8

PMID:37322413

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10273507/

Abstract

BACKGROUND

As an adult tumor with the most invasion and the highest mortality rate, the inherent heterogeneity of glioblastoma (GBM) is the main factor that causes treatment failure. Therefore, it is important to have a deeper understanding of the pathology of GBM. Some studies have shown that Eukaryotic Initiation Factor 4A-3 (EIF4A3) can promote the growth of many people's tumors, and the role of specific molecules in GBM remains unclear.

METHODS

The correlation between the expression of EIF4A3 gene and its prognosis was studied in 94 GBM patients using survival analysis. Further in vitro and in vivo experiments, the effect of EIF4A3 on GBM cells proliferation, migration, and the mechanism of EIF4A3 on GBM was explored. In addition, combined with bioinformatics analysis, we further confirmed that EIF4A3 contributes to the progress of GBM.

RESULTS

The expression of EIF4A3 was upregulated in GBM tissues, and high expression of EIF4A3 is associated with poor prognosis in GBM. In vitro, knockdown of EIF4A3 significantly reduced the proliferation, migration, and invasion abilities of GBM cells, whereas overexpression of EIF4A3 led to the opposite effect. The analysis of differentially expressed genes related to EIF4A3 indicates that it is involved in many cancer-related pathways, such as Notch and JAK-STAT3 signal pathway. In Besides, we demonstrated the interaction between EIF4A3 and Notch1 by RNA immunoprecipitation. Finally, the biological function of EIF4A3-promoted GBM was confirmed in living organisms.

CONCLUSION

The results of this study suggest that EIF4A3 may be a potential prognostic factor, and Notch1 participates in the proliferation and metastasis of GBM cells mediated by EIF4A3.

摘要

背景

作为一种具有最强侵袭性和最高死亡率的成人肿瘤，胶质母细胞瘤（GBM）的固有异质性是导致治疗失败的主要因素。因此，深入了解 GBM 的病理学具有重要意义。一些研究表明，真核起始因子 4A-3（EIF4A3）可以促进许多人的肿瘤生长，而 GBM 中特定分子的作用尚不清楚。

方法

采用生存分析研究了 94 例 GBM 患者中 EIF4A3 基因表达与其预后的相关性。进一步的体外和体内实验，探讨了 EIF4A3 对 GBM 细胞增殖、迁移的影响及其作用机制。此外，结合生物信息学分析，进一步证实了 EIF4A3 促进 GBM 的进展。

结果

EIF4A3 在 GBM 组织中表达上调，EIF4A3 高表达与 GBM 预后不良相关。体外实验中，EIF4A3 敲低显著降低了 GBM 细胞的增殖、迁移和侵袭能力，而过表达 EIF4A3 则导致相反的效果。与 EIF4A3 相关的差异表达基因分析表明，它参与了许多癌症相关途径，如 Notch 和 JAK-STAT3 信号通路。此外，我们通过 RNA 免疫沉淀证实了 EIF4A3 与 Notch1 之间的相互作用。最后，在活体生物体内证实了 EIF4A3 促进 GBM 的生物学功能。