Hou Dianqi, Wang Zhenlin, Li Haimeng, Liu Juan, Liu Yaohua, Jiang Yang, Lou Meiqing
Department of Neurosurgery, Shanghai General Hospital of Nanjing Medical University, Shanghai 201620, China.
Division of Experimental Neurosurgery, Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany.
J Cancer. 2022 Mar 14;13(5):1664-1678. doi: 10.7150/jca.57691. eCollection 2022.
Glioblastoma Multiform (GBM) is the primary malignancy with the highest incidence and worst prognosis in the adult CNS. Circular RNAs (circRNAs) are a novel and widely diverse class of endogenous non-coding RNAs that can promote or inhibit gliomagenesis. Our study aimed to explore the role of circASPM in GBM and its molecular mechanism. Levels of circASPM, miR-130b-3p and E2F1 were determined by quantitative real-time PCR (qRT-PCR) or western blotting assay. MTS, Edu, neurospheres formation and extreme limiting dilution assays were used to detect the tumorigenesis and proliferation of GSCs . The interactions between miR-130b-3p and circASPM or E2F1 were demonstrated via qPCR, western blotting, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft experiments were used to analyze tumor growth . CircASPM was overexpressed in GBM and promoted the tumorigenesis and proliferation of GSCs both and . Mechanistically, circASPM up-regulated the expression of E2F1 in GSCs via miR-130b-3p sponging. We furtherly demonstrated that circAPSM could promote the GSCs proliferation via E2F1 up-regulating. Therefore, our study identified a novel circRNA and its possible mechanism in the development and tumorigenesis of GBM. CircASPM can promote GBM progression via regulating miR-130b-3p/E2F1 axis, suggesting that circAPSM could provide an effective biomarker for GBM diagnosis and prognostic evaluation and possibly being used for molecular targeted therapy.
多形性胶质母细胞瘤(GBM)是成人中枢神经系统中发病率最高、预后最差的原发性恶性肿瘤。环状RNA(circRNAs)是一类新型且种类繁多的内源性非编码RNA,可促进或抑制胶质瘤的发生。我们的研究旨在探讨circASPM在GBM中的作用及其分子机制。通过定量实时PCR(qRT-PCR)或蛋白质免疫印迹法检测circASPM、miR-130b-3p和E2F1的水平。采用MTS、Edu、神经球形成和极限稀释分析来检测胶质瘤干细胞(GSCs)的肿瘤发生和增殖。通过qPCR、蛋白质免疫印迹法、双荧光素酶报告基因和RNA免疫沉淀(RIP)分析证实miR-130b-3p与circASPM或E2F1之间的相互作用。采用异种移植实验分析肿瘤生长情况。circASPM在GBM中过表达,促进了GSCs的肿瘤发生和增殖。机制上,circASPM通过海绵吸附miR-130b-3p上调GSCs中E2F1的表达。我们进一步证明circAPSM可通过上调E2F1促进GSCs增殖。因此,我们的研究确定了一种新型circRNA及其在GBM发生和肿瘤发生中的可能机制。circASPM可通过调节miR-130b-3p/E2F1轴促进GBM进展,提示circAPSM可为GBM诊断和预后评估提供有效的生物标志物,并可能用于分子靶向治疗。