Hui Xu, Yu Cao, Jianqiao Ruan, Fei Wang, Yuhong He, Lina Yang, Tian Yu, Fang Du, Ningmei Zhang, Xiangmei Cao
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Differential gene expression and reference transcription analysis were performed.</p><p><strong>Results: </strong>Successful infection with recombinant lentivirus expressing mutIDH1 was demonstrated. The IDH1 mutation promoted glioma cell migration and invasion while positively regulating the expression of vascularization-related factors and BMP2-related receptors. BMP2 exhibited a positive regulatory effect on the migration, invasion, and angiogenesis of mutIDH1-glioma cells, possibly mediated by BMP2-induced alterations in Smad signaling pathway-related factors.After BMP2 treatment, the differential genes of MutIDH1-glioma cells are closely related to the regulation of cell migration and cell adhesion, especially the regulation of Smad-related proteins. KEGG analysis confirmed that it was related to BMP signaling pathway and TGF-β signaling pathway and cell adhesion. 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引用次数: 0
摘要
目的：本研究探讨了异柠檬酸脱氢酶1（IDH1）突变（mutIDH1）对人类胶质瘤细胞侵袭和血管生成的影响：方法：使用多西环素诱导胶质瘤细胞表达突变IDH1。方法：用强力霉素诱导胶质瘤细胞表达 mutIDH1。用 Western 印迹法和细胞免疫荧光法测定各种蛋白质的表达水平。评估了骨形态发生蛋白2（BMP2）对侵袭的影响、血管生成相关因子、BMP2相关受体的表达以及BMP2处理后Smad信号通路相关蛋白的变化。进行了差异基因表达和参考转录分析：结果：成功感染了表达突变 IDH1 的重组慢病毒。IDH1突变促进了胶质瘤细胞的迁移和侵袭，同时正向调节了血管相关因子和BMP2相关受体的表达。BMP2对mutIDH1-胶质瘤细胞的迁移、侵袭和血管生成具有正向调控作用，可能是由BMP2诱导的Smad信号通路相关因子的改变介导的。BMP2处理后，MutIDH1-胶质瘤细胞的差异基因与细胞迁移和细胞粘附的调控密切相关，尤其是与Smad相关蛋白的调控。KEGG分析证实它与BMP信号通路和TGF-β信号通路以及细胞粘附有关。基因本体和基因组百科的富集分析进一步证实了这些通路的相关性：结论：异柠檬酸脱氢酶1的突变通过影响BMP2驱动的Smad信号通路，促进胶质瘤细胞的迁移、侵袭和血管生成。此外，BMP2改变了突变IDH1胶质瘤细胞的转录模式，丰富了与侵袭、迁移和血管生成相关的通路中的不同基因位点。
The effects of BMP2 and the mechanisms involved in the invasion and angiogenesis of IDH1 mutant glioma cells.
Purpose: This study investigated the effect of an isocitrate dehydrogenase 1 (IDH1) mutation (mutIDH1) on the invasion and angiogenesis of human glioma cells.
Methods: Doxycycline was used to induce the expression of mutIDH1 in glioma cells. Transwell and wound healing assays were conducted to assess glioma cell migration and invasion. Western blotting and cell immunofluorescence were used to measure the expression levels of various proteins. The influence of bone morphogenetic protein 2 (BMP2) on invasion, angiogenesis-related factors, BMP2-related receptor expression, and changes in Smad signaling pathway-related proteins were evaluated after treatment with BMP2. Differential gene expression and reference transcription analysis were performed.
Results: Successful infection with recombinant lentivirus expressing mutIDH1 was demonstrated. The IDH1 mutation promoted glioma cell migration and invasion while positively regulating the expression of vascularization-related factors and BMP2-related receptors. BMP2 exhibited a positive regulatory effect on the migration, invasion, and angiogenesis of mutIDH1-glioma cells, possibly mediated by BMP2-induced alterations in Smad signaling pathway-related factors.After BMP2 treatment, the differential genes of MutIDH1-glioma cells are closely related to the regulation of cell migration and cell adhesion, especially the regulation of Smad-related proteins. KEGG analysis confirmed that it was related to BMP signaling pathway and TGF-β signaling pathway and cell adhesion. Enrichment analysis of gene ontology and genome encyclopedia further confirmed the correlation of these pathways.
Conclusion: Mutation of isocitrate dehydrogenase 1 promotes the migration, invasion, and angiogenesis of glioma cells, through its effects on the BMP2-driven Smad signaling pathway. In addition, BMP2 altered the transcriptional patterns of mutIDH1 glioma cells, enriching different gene loci in pathways associated with invasion, migration, and angiogenesis.
期刊介绍：
The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.
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