Department of Neurosurgery, Changhai Hospital, Naval Medical University, Shanghai, China.
Department of Neurosurgery, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, Hefei, Anhui, China.
Front Immunol. 2024 Jun 28;15:1420182. doi: 10.3389/fimmu.2024.1420182. eCollection 2024.
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.
多形性胶质母细胞瘤（GBM）是最常见的原发性恶性脑肿瘤，以其侵袭性生长和预后不良而臭名昭著。本研究旨在阐明 GBM 的分子基础，特别关注 AGBL4 及其与炎症途径的关系，以发现可行的治疗靶点。
利用单细胞测序来检测 AGBL4 的表达水平，并进行功能测定以评估 AGBL4 调节的影响。
我们的研究结果发现，AGBL4 在 GBM 中显著上调，与不良的临床结局相关。功能测定表明，AGBL4 敲低抑制了 GBM 细胞的增殖、迁移和侵袭，并影响了炎症反应途径，而 AGBL4 过表达则促进了这些活动。进一步的研究表明，AGBL4 通过调节 MMP-1 发挥致癌作用，建立了一个对 GBM 进展和炎症至关重要的新调节轴。
AGBL4 和 MMP-1 都可能是关键的分子靶点，为 GBM 治疗提供了新的靶向治疗途径。
