Guowei Li, Yanping Jin
Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Obstetrics and Gynecology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
Front Neuroinform. 2022 Apr 12;16:859937. doi: 10.3389/fninf.2022.859937. eCollection 2022.
In our research we try to explore whether glioma stem cell containing circRNAs signal pathway could regulate glioma malignant progression and elaborate its possible mechanism.
In this study, we used biological information analysis to build an RNA regulatory network and then proceeded RT-PCR to screen target RNAs, after that we clarified the targeting relationship between circRNA-miRNA-mRNA through double luciferase gene assay, RNA pull down experiment, PCR and Western Blot. Finally we adopted RNA transfection to identify its impact on glioma cell proliferation, invasion, migration, apoptosis and cell cycle.
circ-ASB3 was significantly up-regulated in glioma stem cells compared with glioma cells. The circ-ASB3/miR-543/Twist1 axis was discovered to be a possible regulatory pathway in glioma, circ-ASB3 could adsorb and targeted bind to miR-543, down-regulate miR-543 expression, thus release its targeted inhibition to Twist1. Circ-ASB3 was shown to increase glioma cell proliferation, invasion, and migration miR-543/Twist1 axis. Meanwhile glioma cell apoptosis could be inhibited, and cell cycle arrest could be induced through this signaling pathway.
circ-ASB3 could enhance glioma malignancy miR-543/Twist1 axis, resulting in the discovery of new biomarkers and possible therapeutic targets for these patients.
在我们的研究中,我们试图探索含环状RNA信号通路的胶质瘤干细胞是否能调节胶质瘤的恶性进展,并阐述其可能的机制。
在本研究中,我们利用生物信息分析构建RNA调控网络,然后进行逆转录-聚合酶链反应(RT-PCR)筛选靶RNA,之后通过双荧光素酶基因检测、RNA下拉实验、聚合酶链反应(PCR)和蛋白质免疫印迹法(Western Blot)阐明环状RNA-微小RNA-信使核糖核酸(circRNA-miRNA-mRNA)之间的靶向关系。最后,我们采用RNA转染来确定其对胶质瘤细胞增殖、侵袭、迁移、凋亡和细胞周期的影响。
与胶质瘤细胞相比,环状ASB3(circ-ASB3)在胶质瘤干细胞中显著上调。发现circ-ASB3/miR-543/Twist1轴可能是胶质瘤中的一条调控通路,circ-ASB3可以吸附并靶向结合miR-543,下调miR-543表达,从而解除其对Twist1的靶向抑制。circ-ASB3通过miR-543/Twist1轴增加胶质瘤细胞的增殖、侵袭和迁移。同时,通过该信号通路可抑制胶质瘤细胞凋亡并诱导细胞周期停滞。
circ-ASB3可通过miR-543/Twist1轴增强胶质瘤的恶性程度,从而为这些患者发现新的生物标志物和可能的治疗靶点。