Agrawal Kirti, Chauhan Saumya, Kumar Dhruv
School of Health Sciences and Technology (SoHST), UPES University, Dehradun, Uttarakhand 248007 India.
Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh, Sec 125, Noida, 201303 India.
3 Biotech. 2023 Jan;13(1):10. doi: 10.1007/s13205-022-03419-5. Epub 2022 Dec 15.
GLI gene-mediated hedgehog (Hh) signaling pathway plays a substantial role in brain cancer development and growth including glioblastoma multiforme (GBM), lower-grade glioma (LGG), and medulloblastoma (MB). GLI2 and GLI3 gene expression levels are extremely enhanced in these cancers with poor patient survival. Moreover, GLI genes are correlated with stemness-related factors SOX2, SOX9, POU5F1, and NANOG that work as the driving factors for brain cancer stem cells (CSCs) progression. It's critical to find new ways to combat this deadly malignancy and CSCs. Using in silico approaches, our study explored the role of GLI genes (GLI1, GLI2, and GLI3), the primary transcription factors of the sonic hedgehog (SHH) signaling pathway, in GBM, LGG, MB, and glioblastoma stem-like cells (GSCs). Additionally, we found strong association of angiogenic-related gene VEGFA, metabolic genes ENO1, ENO2, and pluripotency-related genes SOX2, SOX9, NANOG, POU5F1 with GLI genes, suggesting their role in brain tumor initiation and progression. We also studied their transcriptional network and functional category enrichment analysis about brain tumor development to find a better therapeutic strategy against brain cancer and their stem cells.
The online version contains supplementary material available at 10.1007/s13205-022-03419-5.
GLI基因介导的刺猬信号通路（Hh）在包括多形性胶质母细胞瘤（GBM）、低级别胶质瘤（LGG）和髓母细胞瘤（MB）在内的脑癌发生和发展中起重要作用。在这些癌症中，GLI2和GLI3基因表达水平极度增强，患者生存率低。此外，GLI基因与干性相关因子SOX2、SOX9、POU5F1和NANOG相关，这些因子是脑癌干细胞（CSCs）进展的驱动因素。找到对抗这种致命恶性肿瘤和CSCs的新方法至关重要。通过计算机模拟方法，我们的研究探索了GLI基因（GLI1、GLI2和GLI3），即音猬因子（SHH）信号通路的主要转录因子，在GBM、LGG、MB和胶质母细胞瘤样干细胞（GSCs）中的作用。此外，我们发现血管生成相关基因VEGFA、代谢基因ENO1、ENO2以及多能性相关基因SOX2、SOX9、NANOG、POU5F1与GLI基因有很强的关联，表明它们在脑肿瘤起始和进展中的作用。我们还研究了它们关于脑肿瘤发展的转录网络和功能类别富集分析，以找到更好的治疗脑癌及其干细胞的策略。
在线版本包含可在10.1007/s13205-022-03419-5获取的补充材料。
