Yan Manli, Hu Caihong, Hu Qi, Ma Heran, Lei Changjiang, Liu Yamei
Department of Internal Medicine, The Fifth Hospital of Wuhan, Wuhan 430050, China.
Department of Internal Medicine, Wuhan Hospital of China University of Geoscience, Wuhan 430074, China.
Int J Genomics. 2023 Aug 3;2023:1680634. doi: 10.1155/2023/1680634. eCollection 2023.
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.
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.
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.
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.
近期研究表明,环状RNA(circRNAs)与多种疾病的发生或发展有关。在本研究中,我们探讨了circ_0008285在胶质瘤中的潜在作用,并研究了其下游调控因子。
采用定量实时聚合酶链反应检测胶质瘤标本和细胞系中circ_0008285的水平。运用卡方检验评估circ_0008285水平与胶质瘤患者临床特征之间的关系。通过敲低实验研究circ_0008285对胶质瘤细胞增殖和凋亡的作用。同时,在胶质瘤细胞中探讨circ_0008285、miR-384和高迁移率族蛋白B1(HMGB1)之间的调控关系,并研究circ_0008285/miR-384/HMGB1通路对胶质瘤细胞的影响。
在胶质瘤标本和细胞系中,circ_0008285的表达显著增加,且circ_0008285水平高与胶质瘤患者肿瘤体积较大和分级较高相关。此外,下调circ_0008285可抑制胶质瘤细胞的增殖并引发凋亡,这与细胞周期停滞在G1/G0期有关。机制研究表明,circ_0008285通过海绵吸附miR-384来调控HMGB1。功能实验证明,circ_0008285通过miR-384/HMGB1轴促进胶质瘤细胞的恶性表型。
我们的研究揭示了circ_0008285通过调节miR-384/HMGB1通路成为胶质瘤中一种新的致癌因子,表明靶向circ_0008285可能是胶质瘤治疗的一种策略。