EIF4A3 诱导的 Circ_0059914 通过 miR-1249/VEGFA 途径促进神经胶质瘤的血管生成和 EMT。
EIF4A3-Induced Circ_0059914 Promoted Angiogenesis and EMT of Glioma via the miR-1249/VEGFA Pathway.
发表日期:2024 Jul 01
作者:
Wei Yu, Duo Chen, Li Ma, Yuancai Lin, Jihui Zheng, Xinxing Li
来源:
MOLECULAR NEUROBIOLOGY
摘要:
神经胶质瘤是常见的脑肿瘤。尽管进行了广泛的研究,神经胶质瘤的 5 年生存率仍然很低。许多研究报道环状RNA(circRNA)在促进胶质瘤恶性进展中发挥作用;然而,circ_0059914 在此过程中的作用仍不清楚。在本研究中,我们旨在研究circ_0059914在胶质瘤中的功能和潜在机制。使用蛋白质印迹和 qRT-PCR 测定 circ_0059914、miR-1249、VEGFA、N-钙粘蛋白、波形蛋白、Snail 和 EIF4A3 的水平。进行 EDU 和集落形成测定来评估细胞增殖。 Transwell实验用于探索细胞迁移和侵袭,管形成实验用于分析血管生成。 RNA 免疫沉淀 (RIP) 和双荧光素酶报告基因测定用于探索 EIF4A3、circ_0059914、miR-1249 和 VEGFA 之间的关系。进行异种移植肿瘤测定以确定circ_0059914在体内的作用。 Circ_0059914 表达在神经胶质瘤中上调。胶质瘤circ_0059914表达的敲低可减少体内胶质瘤细胞的增殖、迁移、侵袭、上皮间质转化(EMT)、血管生成和生长。 Circ_0059914 吸收 miR-1249,抑制 miR-1249 逆转了胶质瘤细胞中 circ_0059914 敲低介导的作用。发现VEGFA是miR1249的靶基因; VEGFA 的过度表达逆转了神经胶质瘤中 miR-1249 上调的影响。最后,EIF4A3增加了circ_0059914的表达。 EIF4A3 诱导的 circ_0059914 表达通过 miR-1249/VEGFA 轴在促进神经胶质瘤中发挥作用。© 2024。作者获得 Springer Science Business Media, LLC(Springer Nature 的一部分)的独家许可。
Gliomas are common brain tumors. Despite extensive research, the 5-year survival rate of glioma remains low. Many studies have reported that circular RNAs (circRNAs) play a role in promoting the malignant progression of glioma; however, the role of circ_0059914 in this process remains unclear. In this study, we aimed to investigate the function and underlying mechanism of circ_0059914 in glioma. Western blotting and qRT-PCR were used to determine the levels of circ_0059914, miR-1249, VEGFA, N-cadherin, vimentin, Snail, and EIF4A3. EDU and colony formation assays were conducted to evaluate cell proliferation. Transwell assays were used to explore cell migration and invasion and tube formation assays were used to analyze angiogenesis. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were used to explore the relationship between EIF4A3, circ_0059914, miR-1249, and VEGFA. A xenograft tumor assay was performed to determine the role of circ_0059914 in vivo. Circ_0059914 expression was upregulated in gliomas. Knockdown of gliomal circ_0059914 expression reduced the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), angiogenesis, and growth of glioma cells in vivo. Circ_0059914 sponged miR-1249, and miR-1249 inhibition reversed the circ_0059914 knockdown-mediated effects in glioma cells. VEGFA was found to be a target gene of miR1249; overexpression of VEGFA reversed the effect of miR-1249 up-regulation in glioma. Finally, EIF4A3 increased the expression of circ_0059914. EIF4A3-induced circ_0059914 expression plays a role in promoting glioma via the miR-1249/VEGFA axis.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.