Aberrant FoxM1 Expression Increases ASPM Transcription and Promotes the Malignant Properties of Gliomas

Abstract

Gliomas is the most common form of malignant tumor in central nervous system. However, the molecular mechanism of the tumorigenesis and progression of gliomas remains unclear. In this study, we used GEO database to identify genes differentially expressed in gliomas and predict the prognosis of glioma. We observed that ASPM mRNA was increased obviously in glioma tissue, and higher ASPM mRNA expression predicted worse disease prognosis. ASPM was highly expressed in glioma cell lines U87-MG and U251, and knockdown of ASPM expression in these cells significantly repressed the proliferation, migration and invasion ability, and induced G0/G1 phase arrest. In addition, downregulation of ASPM suppressed the growth of glioma in nude mice. Five potential binding sites for transcription factor FoxM1 were predicted in the ASPM promoter. FoxM1 overexpression significantly increased the expression of ASPM and promoted the proliferation and migration of glioma cells, which was abolished by ASPM ablation. ChIP and dual luciferase reporter analysis confirmed that FoxM1 bound to the ASPM promoter at -236~-230bp and -1354~-1348bp and activated the transcription of ASPM directly. Collectively, our results demonstrated for the first time that FoxM1 can directly activate the expression of ASPM at transcription level, and thereby regulating malignant properties of glioma cells. Funding Statement: This work was supported by the National key R&D program (No. 2017YFC0909302), National Natural Science Foundation of China (No.81803582, No.81703622), China Postdoctoral Science Foundation (No.2018M633002) and Hunan Provincial Natural Science Foundation of China (No.2018JJ3838). Declaration of Interests: The authors declare no conflict of interest. Ethical Approval Statement: All procedures were approved by the Ethics Committee of Xiangya Hospital of Central South University, and informed consent was obtained from patients.