肿瘤微环境中的非细胞分泌成分包括趋化因子、细胞因子和生长因子常常发生异常，影响着胶质母细胞瘤（GBM）的形成。目前的治疗对GBM的预后意义仍无令人满意的结果。最近的研究表明，后转录修饰（PTM）及其相应的酶，如乙酰化及泛素化通过调节信号传导事件在GBM的发病机制中具有潜力。然而，目前关于非细胞分泌成分与后转录修饰之间的关系在GBM治疗方面存在研究上的空白。因此，我们旨在通过机器学习和计算生物学方法填补非细胞分泌成分与PTM修饰之间的差距。在本文中，我们强调了BMP1、CTSB、LOX、LOXL1、PLOD1、MMP9、SERPINE1和SERPING1在GBM发病机制中的重要性。此外，我们还证明了E2共轭酶（Ube2E1、Ube2H、Ube2J2、Ube2C、Ube2J2和Ube2S）、E3连接酶（VHL和GNB2L1）与底物（HIF1A）之间的正相关关系。此外，我们报道了由HAT1诱导的Ube2S（K211）和Ube2H（K8、K52）的新的乙酰化位点。关于Ube2S（8）和Ube2H（1）的结构和功能特性研究发现它们与蛋白激酶有关联。最后，我们的结果发现了一个可能的治疗轴HAT1-Ube2S（K211）-GNB2L1-HIF1A和潜在的预测生物标志物（CTSB、HAT1、Ube2H、VHL和GNB2L1），它们在GBM发病机制中起到关键作用。版权所有 © 2023 Kumari和Kumar。

Non-cellular secretory components, including chemokines, cytokines, and growth factors in the tumor microenvironment, are often dysregulated, impacting tumorigenesis in Glioblastoma multiforme (GBM) microenvironment, where the prognostic significance of the current treatment remains unsatisfactory. Recent studies have demonstrated the potential of post-translational modifications (PTM) and their respective enzymes, such as acetylation and ubiquitination in GBM etiology through modulating signaling events. However, the relationship between non-cellular secretory components and post-translational modifications will create a research void in GBM therapeutics. Therefore, we aim to bridge the gap between non-cellular secretory components and PTM modifications through machine learning and computational biology approaches. Herein, we highlighted the importance of BMP1, CTSB, LOX, LOXL1, PLOD1, MMP9, SERPINE1, and SERPING1 in GBM etiology. Further, we demonstrated the positive relationship between the E2 conjugating enzymes (Ube2E1, Ube2H, Ube2J2, Ube2C, Ube2J2, and Ube2S), E3 ligases (VHL and GNB2L1) and substrate (HIF1A). Additionally, we reported the novel HAT1-induced acetylation sites of Ube2S (K211) and Ube2H (K8, K52). Structural and functional characterization of Ube2S (8) and Ube2H (1) have identified their association with protein kinases. Lastly, our results found a putative therapeutic axis HAT1-Ube2S(K211)-GNB2L1-HIF1A and potential predictive biomarkers (CTSB, HAT1, Ube2H, VHL, and GNB2L1) that play a critical role in GBM pathogenesis.Copyright © 2023 Kumari and Kumar.