Chen Fujun, Luo Yong, Lv Fenghong, Li Hongmin
Department of Oncology, People's Hospital of Mingshan District Ya'an, Ya'an, 625100, China.
Department of Neurology, People's Hospital of Mingshan District Ya'an, Ya'an, 625100, China.
J Mol Histol. 2025 Sep 13;56(5):311. doi: 10.1007/s10735-025-10592-3.
Human discs large-associated protein 5 (DLGAP5), also known as DLG7, is a crucial protein associated with the mitotic spindle and is increased in different types of tumours. Nevertheless, its role in glioblastoma (GBM) remain poorly understood. Therefore, the purpose of this work was to examine the mechanisms and biological functions of DLGAP5 in GBM. Furthermore, we investigated how DLGAP5 affected the polarisation of tumor-associated macrophages (TAMs). We assessed the growth, migration, and invasion of GBM cells using a cell counting kit (CCK8), 5-Ethynyl-2'-deoxyuridine (EdU) incorporation, wound healing, and Transwell assays. The expression levels of TAM-associated differentiation markers CD68, CD206, and CD11b were examined by flow cytometry. The effects of tumour cell-derived DLGAP5 on THP-1 macrophage polarisation were investigated using a coculture paradigm including GBM cells and differentiated THP-1 cells. The effect of DLGAP5 on carcinogenesis in vivo was also investigated using a xenograft nude mice model. DLGAP5 was found to be upregulated in both GBM tissues and cell lines. The knockdown of DLGAP5 inhibited GBM cell proliferation, migration, and invasion, as well as M2 polarization of TAMs. In an in vivo model, suppression of DLGAP5 led to decreased tumor growth. Our findings indicate that DLGAP5 significantly promotes the malignant phenotype of GBM. These findings have potential implications for the future diagnosis and therapy of GBM.
人盘大相关蛋白5（DLGAP5），也称为DLG7，是一种与有丝分裂纺锤体相关的关键蛋白，在不同类型的肿瘤中表达增加。然而，其在胶质母细胞瘤（GBM）中的作用仍知之甚少。因此，本研究旨在探讨DLGAP5在GBM中的作用机制和生物学功能。此外，我们还研究了DLGAP5如何影响肿瘤相关巨噬细胞（TAM）的极化。我们使用细胞计数试剂盒（CCK8）、5-乙炔基-2'-脱氧尿苷（EdU）掺入、伤口愈合和Transwell实验评估GBM细胞的生长、迁移和侵袭能力。通过流式细胞术检测TAM相关分化标志物CD68、CD206和CD11b的表达水平。使用包括GBM细胞和分化的THP-1细胞的共培养模式，研究肿瘤细胞来源的DLGAP5对THP-1巨噬细胞极化的影响。还使用异种移植裸鼠模型研究了DLGAP5对体内致癌作用的影响。结果发现，DLGAP5在GBM组织和细胞系中均上调。敲低DLGAP5可抑制GBM细胞增殖、迁移和侵袭，以及TAM的M2极化。在体内模型中，抑制DLGAP5可导致肿瘤生长减缓。我们的研究结果表明，DLGAP5显著促进GBM的恶性表型。这些发现对GBM的未来诊断和治疗具有潜在意义。
