Department of Neurosurgery, The First Hospital of Qinhuangdao, the First Hospital of Qinhuangdao, Qinhuangdao, Hebei, China.
Department of Anesthesiology, Qinglong Manchu Autonomous County Hospital, Qinhuangdao, Hebei, China.
Bioengineered. 2022 Mar;13(3):7541-7552. doi: 10.1080/21655979.2022.2049027.
Glioma is the commonest intracranial malignancy, and circRNAs are important regulatory factors which are implicated in the development of glioma. Nonetheless, the role of circRNAs in glioma is largely unknown. The research is performed to elaborate on the biological role of has_circ_0000418 (circ_0000418) in glioma progression and its potential molecular mechanism. The differentially expressed circRNAs in glioblastoma patient derived cells and neural progenitor cells were analyzed based on the microarray data of GSE146463. Additionally, qRT-PCR and Western blot experiments were conducted to measure the expression of circ_0000418, microRNA-409-3p (miR-409-3p) and pyruvate dehydrogenase kinase 1 () in glioma tissues/cells. Cell growth and cell cycle distribution were monitored using CCK-8 assay, BrdU assay and flow cytometry. Bioinformatics prediction, dual-luciferase reporter gene experiment and RIP assay were conducted to verify the targeting relationship between circ_0000418 and miR-409-3p, miR-409-3p and PDK1 3'UTR. In this work, we observed that, circ_0000418 expression level was significantly up-regulated in glioma tissues and cell lines. Circ_0000418 overexpression facilitated glioma cell growth and accelerated cell cycle progression, while knockdown of circ_0000418 produced the opposite effects. Circ_0000418 specifically combined with miR-409-3p, and circ_0000418 negatively modulated the expression of miR-409-3p. PDK1 acted as a target gene of miR-409-3p, and PDK1 could be positively and indirectly modulated by circ_0000418 in glioma cells. In summary, circ_0000418 enhances glioma cell growth and accelerates cell cycle progression by regulating miR-409-3p/PDK1 axis.
神经胶质瘤是最常见的颅内恶性肿瘤，环状 RNA 是重要的调节因子，参与神经胶质瘤的发生。然而，环状 RNA 在神经胶质瘤中的作用在很大程度上尚不清楚。本研究旨在阐述环状 RNA （circ_0000418）在神经胶质瘤进展中的生物学作用及其潜在的分子机制。根据 GSE146463 的微阵列数据分析神经母细胞瘤患者来源细胞和神经祖细胞中差异表达的环状 RNA。此外，通过 qRT-PCR 和 Western blot 实验测量神经胶质瘤组织/细胞中 circ_0000418、微小 RNA-409-3p（miR-409-3p）和丙酮酸脱氢酶激酶 1（）的表达。通过 CCK-8 测定、BrdU 测定和流式细胞术监测细胞生长和细胞周期分布。通过生物信息学预测、双荧光素酶报告基因实验和 RIP 实验验证 circ_0000418 与 miR-409-3p、miR-409-3p 与 PDK1 3'UTR 的靶向关系。在这项工作中，我们观察到 circ_0000418 在神经胶质瘤组织和细胞系中的表达水平显著上调。circ_0000418 的过表达促进神经胶质瘤细胞生长并加速细胞周期进程，而 circ_0000418 的敲低则产生相反的效果。circ_0000418 特异性结合 miR-409-3p，circ_0000418 负调控 miR-409-3p 的表达。PDK1 作为 miR-409-3p 的靶基因，在神经胶质瘤细胞中，PDK1 可被 circ_0000418 正向间接调节。总之，circ_0000418 通过调节 miR-409-3p/PDK1 轴增强神经胶质瘤细胞的生长并加速细胞周期进程。
