FOXM1 Upregulates O-GlcNAcylation Level Via The Hexosamine Biosynthesis Pathway to Promote Angiogenesis in Hepatocellular Carcinoma.

IF 1.8 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Biochemistry and Biophysics Pub Date : 2024-09-01 Epub Date: 2024-07-20 DOI:10.1007/s12013-024-01393-8

Xiaorong Zhang, Yifan Zhong, Qing Yang

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引用次数: 0

Abstract

Hepatocellular carcinoma (HCC) presents significant challenges in treatment and prognosis because of its aggressive nature and high metastatic potential. This study aims to investigate the role of the hexosamine biosynthesis pathway (HBP) and its association with HCC progression and prognosis. We identified SPP1 and FOXM1 as hub genes within the HBP pathway, showing their correlation with poor prognosis and late-stage progression. In addition, the analysis uncovered the complex participation of the HBP pathway in nutrients and oxygen reactions, PI3K-AKT signaling, AMPK activation, and angiogenesis regulation. The disruption of these pathways is pivotal in influencing the growth and progression of HCC. Targeting the HBP presents a promising therapeutic approach to modulate the tumor microenvironment, thereby enhancing the efficacy of immunotherapy. In addition, FOXM1 was identified as the HBP pathway regulator, influencing cellular O-GlcNAcylation level and VEGF secretion, thereby promoting angiogenesis in HCC. Inhibition of O-GlcNAcylation significantly hindered angiogenesis, which is suggested as a potential avenue for therapeutic intervention. Our research demonstrates the practicality of using the HBP-related gene as a prognostic marker in liver cancer patients and suggests targeting FOXM1 as a novel avenue for personalized therapy.

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FOXM1 通过六胺生物合成途径上调 O-GlcNAcylation 水平，促进肝细胞癌的血管生成

肝细胞癌（HCC）具有侵袭性和高度转移性，给治疗和预后带来了巨大挑战。本研究旨在探讨己胺生物合成途径（HBP）的作用及其与 HCC 进展和预后的关系。我们发现 SPP1 和 FOXM1 是 HBP 通路中的枢纽基因，它们与不良预后和晚期进展相关。此外，分析还发现 HBP 通路复杂地参与了营养和氧反应、PI3K-AKT 信号转导、AMPK 激活和血管生成调控。这些通路的破坏是影响 HCC 生长和进展的关键。以 HBP 为靶点是一种很有前景的治疗方法，可以调节肿瘤微环境，从而提高免疫疗法的疗效。此外，研究还发现 FOXM1 是 HBP 通路的调节因子，可影响细胞的 O-GlcNAcylation 水平和 VEGF 分泌，从而促进 HCC 的血管生成。抑制O-GlcNAcylation会明显阻碍血管生成，这被认为是一种潜在的治疗干预途径。我们的研究证明了将HBP相关基因作为肝癌患者预后标志物的实用性，并建议将靶向FOXM1作为个性化治疗的新途径。

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来源期刊

Cell Biochemistry and Biophysics 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

7.5 months

期刊介绍： Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.