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环状 RNA-SMO 通过海绵吸附 miR-326 上调 CEP85 促进脑胶质瘤的增殖和迁移。

circRNA-SMO upregulates CEP85 to promote proliferation and migration of glioblastoma via sponging miR-326.

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Medical College of Zhejiang University, Hangzhou, Zhejiang Province, China.

Department of Neurosurgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China.

出版信息

Histol Histopathol. 2023 Nov;38(11):1307-1319. doi: 10.14670/HH-18-587. Epub 2023 Jan 18.

DOI:10.14670/HH-18-587
PMID:36718820
Abstract

Circular RNAs (circRNAs) play an important role in cancer development by sponging microRNAs (miRNAs) to regulate the signaling axis. However, more comprehensive mechanisms of circRNAs in glioblastoma need to be elucidated. RT-qPCR was used to detect the expression levels of circRNA-SMO and miR-326. Dual-luciferase reporter assays were conducted to verify the interaction among circRNA-SMO, miR-326, and CEP85. Flow cytometric analysis was performed to detect apoptosis. Western blotting was used to determine the protein levels of the different molecules. Animal xenograft experiments were performed to evaluate the role of circRNA-SMO in vivo. CircRNA-SMO was upregulated in glioblastoma tissues and glioblastoma cells. CircRNA-SMO downregulation inhibited the viability and colony-forming ability of the glioblastoma cells. In addition, miR-326 was downregulated in glioblastoma cells, which was verified to sponge circRNA-SMO and interact with CEP85. Moreover, circRNA-SMO inhibition induced the elevation of miR-326 and apoptosis, accompanied by a decrease in CEP85. CircRNA-SMO knockdown-mediated tumor inhibition was prevented by an miR-326 inhibitor. Furthermore, circRNA-SMO inhibition inhibited tumor growth in vivo, accompanied by an increase in miR-326 and a decline in CEP85 in tumor tissues. Conclusions. CircRNA-SMO sponges miR-326 to promote glioblastoma proliferation and migration by upregulating CEP85 expression. This study clarified the role of circRNA-SMO in the development of glioblastoma, providing novel insights for its treatment.

摘要

环状 RNA(circRNA)通过海绵 microRNA(miRNA)来调节信号轴,在癌症发展中发挥重要作用。然而,需要阐明 circRNA 在神经胶质瘤中更全面的机制。使用 RT-qPCR 检测 circRNA-SMO 和 miR-326 的表达水平。进行双荧光素酶报告基因实验验证 circRNA-SMO、miR-326 和 CEP85 之间的相互作用。通过流式细胞术分析检测细胞凋亡。使用 Western blot 检测不同分子的蛋白水平。进行动物异种移植实验以评估 circRNA-SMO 在体内的作用。circRNA-SMO 在神经胶质瘤组织和神经胶质瘤细胞中上调。circRNA-SMO 下调抑制神经胶质瘤细胞的活力和集落形成能力。此外,miR-326 在神经胶质瘤细胞中下调,被验证为海绵吸附 circRNA-SMO 并与 CEP85 相互作用。此外,circRNA-SMO 抑制诱导 miR-326 的升高和细胞凋亡,同时 CEP85 减少。circRNA-SMO 抑制介导的肿瘤抑制作用被 miR-326 抑制剂所阻止。此外,circRNA-SMO 抑制抑制体内肿瘤生长,同时肿瘤组织中 miR-326 增加和 CEP85 减少。结论。circRNA-SMO 通过上调 CEP85 表达来海绵吸附 miR-326,促进神经胶质瘤的增殖和迁移。本研究阐明了 circRNA-SMO 在神经胶质瘤发生发展中的作用,为其治疗提供了新的思路。

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