AGBL4 通过调节 MMP-1 和炎症途径促进胶质母细胞瘤的恶性进展。
AGBL4 promotes malignant progression of glioblastoma via modulation of MMP-1 and inflammatory pathways.
发表日期:2024
作者:
Shuai Zhang, Lilin Cheng, Yandong Su, Zhongrun Qian, Zhen Wang, Chao Chen, Rong Li, Aikang Zhang, Jiawei He, Jiangxin Mao, Hongxiang Wang, Juxiang Chen
来源:
Brain Structure & Function
摘要:
多形性胶质母细胞瘤(GBM)是最常见的原发性恶性脑肿瘤,因其侵袭性生长和不良预后而臭名昭著。本研究旨在阐明 GBM 的分子基础,特别关注 AGBL4 的作用及其与炎症通路的联系,以发现可行的治疗靶点。利用单细胞测序来检查 AGBL4 的表达水平,并进行功能分析评估 AGBL4 调节的影响。我们的研究结果发现 GBM 中 AGBL4 显着上调,这与不良临床结果相关。功能分析表明,AGBL4 敲低抑制 GBM 细胞增殖、迁移和侵袭,并影响炎症反应途径,而 AGBL4 过表达则促进这些活性。进一步的研究表明,AGBL4通过调节MMP-1发挥其致癌作用,建立了对GBM进展和炎症至关重要的新调控轴。AGBL4和MMP-1可能是关键的分子靶点,为GBM治疗的靶向治疗提供了新途径。版权所有 © 2024 张、程、苏、钱、王、陈、李、张、何、毛、王、陈。
Glioblastoma multiforme (GBM), the most common primary malignant brain tumor, is notorious for its aggressive growth and dismal prognosis. This study aimed to elucidate the molecular underpinnings of GBM, particularly focusing on the role of AGBL4 and its connection to inflammatory pathways, to discover viable therapeutic targets.Single-cell sequencing was utilized to examine the expression levels of AGBL4 and functional assays were performed to assess the effects of AGBL4 modulation.Our findings identified the significant upregulation of AGBL4 in GBM, which correlated with adverse clinical outcomes. Functional assays demonstrated that AGBL4 knockdown inhibited GBM cell proliferation, migration, and invasion and influenced inflammatory response pathways, while AGBL4 overexpression promoted these activities. Further investigation revealed that AGBL4 exerted its oncogenic effects through modulation of MMP-1, establishing a novel regulatory axis critical for GBM progression and inflammation.Both AGBL4 and MMP-1 may be pivotal molecular targets, offering new avenues for targeted therapy in GBM management.Copyright © 2024 Zhang, Cheng, Su, Qian, Wang, Chen, Li, Zhang, He, Mao, Wang and Chen.