Abstract：
BACKGROUND: Glioblastoma is one of the most aggressive tumors. The etiology and the factors determining its onset are not yet entirely known. This study investigates the origins of GBM, and for this purpose, it focuses primarily on developmental gliogenic processes. It also focuses on the impact of the related neurogenic developmental processes in glioblastoma oncogenesis. It also addresses why glial cells are at more risk of tumor development compared to neurons.
METHODS: Databases including PubMed, MEDLINE, and Google Scholar were searched for published articles without any date restrictions, involving glioblastoma, gliogenesis, neurogenesis, stemness, neural stem cells, gliogenic signaling and pathways, neurogenic signaling and pathways, and astrocytogenic genes.
RESULTS: The origin of GBM is dependent on dysregulation in multiple genes and pathways that accumulatively converge the cells towards oncogenesis. There are multiple layers of steps in glioblastoma oncogenesis including the failure of cell fate-specific genes to keep the cells differentiated in their specific cell types such as p300, BMP, HOPX, and NRSF/REST. There are genes and signaling pathways that are involved in differentiation and also contribute to GBM such as FGFR3, JAK-STAT, and hey1. The genes that contribute to differentiation processes but also contribute to stemness in GBM include notch, Sox9, Sox4, c-myc gene overrides p300, and then GFAP, leading to upregulation of nestin, SHH, NF-κB, and others. GBM mutations pathologically impact the cell circuitry such as the interaction between Sox2 and JAK-STAT pathway, resulting in GBM development and progression.
CONCLUSIONS: Glioblastoma originates when the gene expression of key gliogenic genes and signaling pathways become dysregulated. This study identifies key gliogenic genes having the ability to control oncogenesis in glioblastoma cells, including p300, BMP, PAX6, HOPX, NRSF/REST, LIF, and TGF beta. It also identifies key neurogenic genes having the ability to control oncogenesis including PAX6, neurogenins including Ngn1, NeuroD1, NeuroD4, Numb, NKX6-1 Ebf, Myt1, and ASCL1. This study also postulates how aging contributes to the onset of glioblastoma by dysregulating the gene expression of NF-κB, REST/NRSF, ERK, AKT, EGFR, and others.
METHODS: Databases including PubMed, MEDLINE, and Google Scholar were searched for published articles without any date restrictions, involving glioblastoma, gliogenesis, neurogenesis, stemness, neural stem cells, gliogenic signaling and pathways, neurogenic signaling and pathways, and astrocytogenic genes.
RESULTS: The origin of GBM is dependent on dysregulation in multiple genes and pathways that accumulatively converge the cells towards oncogenesis. There are multiple layers of steps in glioblastoma oncogenesis including the failure of cell fate-specific genes to keep the cells differentiated in their specific cell types such as p300, BMP, HOPX, and NRSF/REST. There are genes and signaling pathways that are involved in differentiation and also contribute to GBM such as FGFR3, JAK-STAT, and hey1. The genes that contribute to differentiation processes but also contribute to stemness in GBM include notch, Sox9, Sox4, c-myc gene overrides p300, and then GFAP, leading to upregulation of nestin, SHH, NF-κB, and others. GBM mutations pathologically impact the cell circuitry such as the interaction between Sox2 and JAK-STAT pathway, resulting in GBM development and progression.
CONCLUSIONS: Glioblastoma originates when the gene expression of key gliogenic genes and signaling pathways become dysregulated. This study identifies key gliogenic genes having the ability to control oncogenesis in glioblastoma cells, including p300, BMP, PAX6, HOPX, NRSF/REST, LIF, and TGF beta. It also identifies key neurogenic genes having the ability to control oncogenesis including PAX6, neurogenins including Ngn1, NeuroD1, NeuroD4, Numb, NKX6-1 Ebf, Myt1, and ASCL1. This study also postulates how aging contributes to the onset of glioblastoma by dysregulating the gene expression of NF-κB, REST/NRSF, ERK, AKT, EGFR, and others.
摘要：
背景：胶质母细胞瘤是最具侵袭性的肿瘤之一。病因和决定其发病的因素尚不完全清楚。本研究调查了GBM的起源，为此，它主要集中在发育的胶质生成过程。它还着重于胶质母细胞瘤肿瘤发生中相关神经源性发育过程的影响。它还解释了为什么神经胶质细胞与神经元相比具有更高的肿瘤发展风险。
方法：包括PubMed、MEDLINE,谷歌学者在没有任何日期限制的情况下搜索已发表的文章，涉及胶质母细胞瘤，胶质发生，神经发生，stemness,神经干细胞,胶质信号和途径，神经源性信号和通路，和星形细胞基因。
结果：GBM的起源依赖于多个基因和途径的失调，这些基因和途径使细胞向肿瘤发生方向聚集。胶质母细胞瘤肿瘤发生有多个步骤，包括细胞命运特异性基因的失败，以保持细胞在其特定细胞类型中分化，如p300，BMP，HOPX,和NRSF/REST。有基因和信号通路参与分化，也有助于GBM，如FGFR3，JAK-STAT，hey1。在GBM中有助于分化过程但也有助于干性的基因包括notch，Sox9，Sox4，c-myc基因覆盖p300，然后是GFAP，导致巢蛋白的上调，SHH,NF-κB,和其他人。GBM突变在病理上影响细胞回路，例如Sox2和JAK-STAT通路之间的相互作用，导致GBM的发展和进步。
结论：胶质母细胞瘤起源于关键胶质细胞生成基因和信号通路的基因表达失调。这项研究确定了关键的胶质细胞生成基因具有控制胶质母细胞瘤细胞中肿瘤发生的能力，包括p300、BMP、PAX6,HOPX,NRSF/REST,LIF,和TGFβ。它还确定了具有控制肿瘤发生的能力的关键神经基因，包括PAX6，包括Ngn1，NeuroD1，NeuroD4，Numb，NKX6-1Ebf,Myt1和ASCL1。这项研究还假设衰老如何通过调节NF-κB的基因表达而导致胶质母细胞瘤的发作。REST/NRSF,ERK,AKT,EGFR,和其他人。
方法：包括PubMed、MEDLINE,谷歌学者在没有任何日期限制的情况下搜索已发表的文章，涉及胶质母细胞瘤，胶质发生，神经发生，stemness,神经干细胞,胶质信号和途径，神经源性信号和通路，和星形细胞基因。
结果：GBM的起源依赖于多个基因和途径的失调，这些基因和途径使细胞向肿瘤发生方向聚集。胶质母细胞瘤肿瘤发生有多个步骤，包括细胞命运特异性基因的失败，以保持细胞在其特定细胞类型中分化，如p300，BMP，HOPX,和NRSF/REST。有基因和信号通路参与分化，也有助于GBM，如FGFR3，JAK-STAT，hey1。在GBM中有助于分化过程但也有助于干性的基因包括notch，Sox9，Sox4，c-myc基因覆盖p300，然后是GFAP，导致巢蛋白的上调，SHH,NF-κB,和其他人。GBM突变在病理上影响细胞回路，例如Sox2和JAK-STAT通路之间的相互作用，导致GBM的发展和进步。
结论：胶质母细胞瘤起源于关键胶质细胞生成基因和信号通路的基因表达失调。这项研究确定了关键的胶质细胞生成基因具有控制胶质母细胞瘤细胞中肿瘤发生的能力，包括p300、BMP、PAX6,HOPX,NRSF/REST,LIF,和TGFβ。它还确定了具有控制肿瘤发生的能力的关键神经基因，包括PAX6，包括Ngn1，NeuroD1，NeuroD4，Numb，NKX6-1Ebf,Myt1和ASCL1。这项研究还假设衰老如何通过调节NF-κB的基因表达而导致胶质母细胞瘤的发作。REST/NRSF,ERK,AKT,EGFR,和其他人。
