FoxM1 regulates Sirt1 expression in glioma cells

G.-Y. Zhu, B.-Z. Shi, Y. Li

Department of Neurosurgery, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China. sbzmd20569@163.com

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• Oncology

BACKGROUND AND OBJECTIVES: Glioma accounts for most of primary malignant brain tumors and usually results in poor survival. However, the key signaling networks regulating glioma cell proliferation remain poorly defined. The forkhead box M1 (FoxM1) is a key transcription factor regulating multiple aspects of cell biology. Prior studies have shown that FoxM1 is overexpressed in glioma and plays a critical role in cancer development and progression.

MATERIALS AND METHODS: Western blot and Real-time PCR assays were used to determine the regulation roles of FoxM1 on Sirt1 (Sirtuin1) expression. Small interfering RNAs (siRNAs) were used to silence the expression of FoxM1. Luciferase assays were used to measure binding of FoxM1 to the promoter region of Sirt1. Direct binding of FoxM1 to promoter of Sirt1 was assessed by chromatin immunoprecipitation (CHIP) assays.

RESULTS: We found that FoxM1 positively regulated mRNA expression of Sirt1. FoxM1 overexpression promoted while its knockdown inhibited Sirt1 expression. Besides, we identified a minimal FoxM1 binding site on the promoter region of Sirt1.

CONCLUSIONS: Our results for the first time add a new FoxM1-Sirt1 connection that mediates cell proliferation in glioma.

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