EIF4A3诱导的circGRIK2通过调控miR-1303/HOXA10轴促进胶质瘤的恶性发展。

EIF4A3 induced circGRIK2 promotes the malignancy of glioma by regulating the miR-1303/HOXA10 axis.

作者信息

Li Fubin, Song Wei, Wu Lin, Liu Bin, Du Xinrui

机构信息

Department of Neurosurgery, Zibo Central Hospital Zibo 255036, Shandong, China.

Department of Breast and Thyroid Surgery, Zibo Central Hospital Zibo 255036, Shandong, China.

出版信息

Am J Cancer Res. 2023 Dec 15;13(12):5868-5886. eCollection 2023.

DOI:
Abstract

In recent years, the role of circular RNAs (circRNAs) in glioma has become increasingly important. However, there are still many newly discovered circRNAs with unknown functions that require further study. In this study, circRNA sequencing, qPCR, MTS, EdU, Transwell, and other assays were conducted to detect the expression and malignant effects of a novel circRNA molecule, circGRIK2, in glioma. qPCR, western blotting, RIP, and luciferase reporter gene experiments were used to investigate the downstream molecular mechanisms of circGRIK2. Our study found that circGRIK2 was highly expressed in glioma and promoted glioma cell viability, proliferation, invasion, and migration. Mechanistically, circGRIK2 acted as a competitive sponge for miR-1303, upregulating the expression of HOXA10 to exert its oncogenic effects. Additionally, the RNA-binding protein EIF4A3 could bind to and stabilize circGRIK2, leading to its high expression in glioblastoma. The discovery of circGRIK2 in this study not only contributes to a better understanding of the biological mechanisms of circGRIK2 in glioma but also provides a new target for molecular targeted therapy.

摘要

近年来,环状RNA(circRNA)在胶质瘤中的作用变得越来越重要。然而,仍有许多新发现的功能未知的circRNA需要进一步研究。在本研究中,进行了circRNA测序、qPCR、MTS、EdU、Transwell等实验,以检测一种新型circRNA分子circGRIK2在胶质瘤中的表达及其恶性影响。采用qPCR、蛋白质免疫印迹、RNA免疫沉淀和荧光素酶报告基因实验来研究circGRIK2的下游分子机制。我们的研究发现,circGRIK2在胶质瘤中高表达,并促进胶质瘤细胞的活力、增殖、侵袭和迁移。机制上,circGRIK2作为miR-1303的竞争性海绵,上调HOXA10的表达以发挥其致癌作用。此外,RNA结合蛋白EIF4A3可以结合并稳定circGRIK2,导致其在胶质母细胞瘤中高表达。本研究中circGRIK2的发现不仅有助于更好地理解circGRIK2在胶质瘤中的生物学机制,也为分子靶向治疗提供了新的靶点。

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