Aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the progression of gliomas.
Aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the progression of gliomas.
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FoxM1转录调控介导的异常ASPM表达促进神经胶质瘤的进展
DOI：
10.1111/jcmm.15435
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发表时间：
2020-09
影响因子：
5.3
通讯作者：
Chen XP
中科院分区：
文献类型：
--
作者：
Zeng WJ;Cheng Q;Wen ZP;Wang JY;Chen YH;Zhao J;Gong ZC;Chen XP
神经胶质瘤是中枢神经系统最常见的恶性肿瘤。然而，胶质瘤发生和发展的分子机制仍不清楚。在这项研究中，我们使用GEO数据库来识别胶质瘤中差异表达的基因，并预测胶质瘤的预后。我们观察到ASPM mRNA在胶质瘤组织中明显增高，且ASPM mRNA表达越高，预后越差。ASPM在胶质瘤细胞系U87-MG和U251中高表达，下调ASPM表达可显著抑制细胞的增殖、迁移和侵袭能力，并诱导G 0/G1期阻滞。此外，ASPM的下调抑制了裸鼠中胶质瘤的生长。在ASPM启动子中预测了转录因子FoxM 1的5个潜在结合位点。FoxM 1过表达可显著增加ASPM的表达，促进胶质瘤细胞的增殖和迁移，ASPM消融可抑制FoxM 1过表达。ChIP和双荧光素酶报告基因分析证实，FoxM 1与ASPM启动子在−236至− 230 bp和−1354至− 1348 bp处结合，并直接激活ASPM的转录。总的来说，我们的研究结果首次表明，ASPM表达异常介导的转录调控FoxM 1促进胶质瘤细胞的恶性性质。
Gliomas are the most common form of malignant tumour in the central nervous system. However, the molecular mechanism of the tumorigenesis and progression of gliomas remains unclear. In this study, we used the 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, down‐regulation 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 to ‐230 bp and −1354 to ‐1348 bp and activated the transcription of ASPM directly. Collectively, our results demonstrated for the first time that aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the malignant properties of glioma cells.
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DOI：
10.1007/s00018-017-2714-7
发表时间：
2018-03
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Meel MH;Schaper SA;Kaspers GJL;Hulleman E
通讯作者：
Hulleman E
影响因子：
56.9
作者：
KOFF, A;GIORDANO, A;ROBERTS, JM
通讯作者：
ROBERTS, JM
影响因子：
21.3
作者：
Laoukili, J;Kooistra, MRH;Medema, RH
通讯作者：
Medema, RH
影响因子：
5.8
作者：
Novorol C;Burkhardt J;Wood KJ;Iqbal A;Roque C;Coutts N;Almeida AD;He J;Wilkinson CJ;Harris WA
通讯作者：
Harris WA
DOI：
10.1016/j.bbagrm.2014.11.008
发表时间：
2015-03-01
影响因子：
4.7
作者：
Hu, Chang-Jiang;Wang, Bin;Yang, Shi-Ming
通讯作者：
Yang, Shi-Ming