Zhu G-Y, Shi B-Z, Li Y
Department of Neurosurgery, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China.
Eur Rev Med Pharmacol Sci. 2014;18(2):205-11.
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.
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.
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.
Our results for the first time add a new FoxM1-Sirt1 connection that mediates cell proliferation in glioma.
胶质瘤占原发性恶性脑肿瘤的大多数，通常导致生存率低下。然而，调节胶质瘤细胞增殖的关键信号网络仍不清楚。叉头框M1（FoxM1）是一种调节细胞生物学多个方面的关键转录因子。先前的研究表明，FoxM1在胶质瘤中过表达，并在癌症发展和进展中起关键作用。
采用蛋白质免疫印迹法和实时定量聚合酶链反应检测FoxM1对沉默信息调节因子1（Sirt1）表达的调控作用。使用小干扰RNA（siRNA）沉默FoxM1的表达。荧光素酶报告基因检测用于检测FoxM1与Sirt1启动子区域的结合。通过染色质免疫沉淀（CHIP）检测评估FoxM1与Sirt1启动子的直接结合。
我们发现FoxM1正向调节Sirt1的mRNA表达。FoxM1过表达促进而其敲低抑制Sirt1表达。此外，我们在Sirt1启动子区域鉴定出一个最小的FoxM1结合位点。
我们的结果首次增加了一种新的FoxM1-Sirt1联系，其介导胶质瘤中的细胞增殖。
