circ_0008285 Regulates Glioma Progression via the miR-384/HMGB1 Axis

Manli Yan, Caihong Hu, Qi Hu, Heran Ma, Changjiang Lei, Yamei Liu
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Abstract

Background. Recent studies indicate that circular RNAs (circRNAs) have been implicated in the initiation or progression of a wide spectrum of diseases. In the current study, we explored the potential engagement of circ_0008285 in glioma and investigated the downstream regulators. Methods. The detection of circ_0008285 level in glioma specimens and cell lines was conducted by quantitative real-time polymerase chain reaction. The chi-squared test was employed to evaluate the relationship between the circ_0008285 level and the clinical features of glioma patients. The roles of circ_0008285 on the proliferation and apoptosis of glioma cells were studied by knockdown experiment. Meanwhile, the regulatory relationship of circ_0008285, miR-384, and high mobility group protein B1 (HMGB1) was explored in glioma cells, and we explored the effects of circ_0008285/miR-384/HMGB1 pathway on glioma cells. Results. In glioma specimens and cell lines, the expression of circ_0008285 was significantly increased, and a high circ_0008285 level was associated with a larger tumor size and more advanced grading in glioma patients. Furthermore, downregulating circ_0008285 suppressed proliferation and triggered apoptosis of glioma cells, which was associated with a cell cycle arrest at the G1/G0 phase. Mechanism studies indicated that circ_0008285 regulated HMGB1 by sponging miR-384. Functional experiments demonstrated that circ_0008285 promoted the malignant phenotype of glioma cells by miR-384/HMGB1 axis. Conclusion. Our study revealed circ_0008285 as a novel oncogenic factor in glioma through modulating the miR-384/HMGB1 pathway, suggesting that targeting circ_0008285 could serve as a strategy for glioma management.

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circ_0008285通过miR-384/HMGB1轴调控胶质瘤进展。
背景:最近的研究表明,环状rna (circRNAs)与多种疾病的发生或进展有关。在目前的研究中,我们探索了circ_0008285在胶质瘤中的潜在作用,并研究了下游调节因子。方法:采用实时定量聚合酶链反应法检测胶质瘤标本和细胞系中circ_0008285的水平。采用卡方检验评价circ_0008285水平与胶质瘤患者临床特征的关系。通过敲除实验研究circ_0008285在胶质瘤细胞增殖和凋亡中的作用。同时探索circ_0008285、miR-384、高迁移率组蛋白B1 (HMGB1)在胶质瘤细胞中的调控关系,探讨circ_0008285/miR-384/HMGB1通路对胶质瘤细胞的影响。结果:在胶质瘤标本和细胞系中,circ_0008285的表达显著增加,且circ_0008285的高表达水平与胶质瘤患者的肿瘤大小和分级更高级相关。此外,下调circ_0008285抑制胶质瘤细胞的增殖并引发细胞凋亡,这与细胞周期阻滞在G1/G0期有关。机制研究表明circ_0008285通过海绵化miR-384调控HMGB1。功能实验证实circ_0008285通过miR-384/HMGB1轴促进胶质瘤细胞的恶性表型。结论:我们的研究表明circ_0008285通过调节miR-384/HMGB1通路在胶质瘤中是一种新的致癌因子,这表明靶向circ_0008285可以作为胶质瘤治疗的一种策略。
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Comparative and Functional Genomics
Comparative and Functional Genomics 生物-生化与分子生物学
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