Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Cell Death Dis. 2022 Aug 18;13(8):721. doi: 10.1038/s41419-022-05127-7.
Glioblastoma (GBM) is one of the most malignant types of brain cancer. Tumor treating fields (TTFields) is the up-to-date treatment for GBM. However, its molecular mechanism requires additional investigation. Herein, a novel TTFields system was developed (CL-301A) and its efficiency in suppressing GBM cell proliferation and inducing cell apoptosis was demonstrated. Through the whole proteomic and transcriptomic analyses, a multitude of differentially expressed proteins (1243), mRNAs (4191), miRtNAs (47), lncRNAs (4286), and circRNAs (13,903) were identified. Bioinformatic analysis indicated that TTFields mainly affected nuclear proteins and interrupt cell mitosis-related events. Moreover, the inhibition of autophagy could significantly enhance the anti-GBM activity of TTFields. And CDK2-AS1 might be a target of TTFields to mediate cell cycle arrest via regulating CDK2 mRNA stability. This study provided valuable resources for understanding the mechanism of TTFields, which might further assist the investigation of TTFields in GBM treatment.
胶质母细胞瘤（GBM）是最恶性的脑癌类型之一。肿瘤治疗电场（TTFields）是目前治疗 GBM 的方法。然而，其分子机制仍需要进一步研究。本文构建了一种新型 TTFields 系统（CL-301A），并证明其能够有效抑制 GBM 细胞增殖并诱导细胞凋亡。通过全蛋白质组学和转录组学分析，鉴定出了大量差异表达的蛋白质（1243 种）、mRNA（4191 种）、miRtNAs（47 种）、lncRNAs（4286 种）和 circRNAs（13903 种）。生物信息学分析表明，TTFields 主要影响核蛋白，并中断细胞有丝分裂相关事件。此外，抑制自噬可以显著增强 TTFields 的抗 GBM 活性。CDK2-AS1 可能是 TTFields 的作用靶点，通过调节 CDK2 mRNA 的稳定性来介导细胞周期停滞。本研究为了解 TTFields 的作用机制提供了有价值的资源，可能进一步有助于 TTFields 在 GBM 治疗中的研究。
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