Xie Shao, Ding Jiahai, Wang Zhaohao, Shi Hengliang, Yu Zheng-Quan
Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Front Genet. 2025 Jan 29;16:1518573. doi: 10.3389/fgene.2025.1518573. eCollection 2025.
Glioma, a primary intracranial tumor, is marked by high rates of mortality and disability, making it a significant health concern. Understanding the molecular mechanisms underlying glioma initiation and progression and identifying potential therapeutic targets for gene therapy are crucial for improving patient outcomes. Golgi phosphoprotein 3 (GOLPH3), predominantly localized at the trans-Golgi network, has been implicated in the pathogenesis of various cancers. However, its precise role in glioma progression remains under active investigation.
To elucidate the function of GOLPH3, U87 glioma cells were transfected with GOLPH3-specific small interfering RNA (siRNA) to suppress its expression. An glioma model was generated by implanting GOLPH3-knockdown U87 cells into nude mice. Apoptosis was assessed using flow cytometry, immunofluorescence staining, TUNEL assays, and Western blotting. The activation of the JNK signaling pathway was evaluated by analyzing the phosphorylation levels of JNK and c-Jun through Western blotting.
Downregulation of GOLPH3 in U87 glioma cells significantly enhanced apoptosis, as evidenced by increased levels of cleaved caspase-3 and higher apoptosis rates. Furthermore, GOLPH3 knockdown led to the activation of the JNK signaling pathway, as indicated by elevated phosphorylation of JNK and c-Jun. , suppression of GOLPH3 expression inhibited tumor growth and increased apoptosis within the tumor microenvironment.
These findings suggest that GOLPH3 might play a pivotal role in regulating apoptosis in malignant glioma cells via the JNK signaling pathway. Thus, GOLPH3 may represent a promising therapeutic target for glioma treatment.
胶质瘤是一种原发性颅内肿瘤，死亡率和致残率很高，是一个重大的健康问题。了解胶质瘤发生和发展的分子机制，并确定基因治疗的潜在靶点，对于改善患者预后至关重要。高尔基体磷蛋白3（GOLPH3）主要定位于反式高尔基体网络，与多种癌症的发病机制有关。然而，其在胶质瘤进展中的精确作用仍在积极研究中。
为了阐明GOLPH3的功能，用GOLPH3特异性小干扰RNA（siRNA）转染U87胶质瘤细胞以抑制其表达。通过将GOLPH3敲低的U87细胞植入裸鼠体内建立胶质瘤模型。使用流式细胞术、免疫荧光染色、TUNEL检测和蛋白质印迹法评估细胞凋亡。通过蛋白质印迹法分析JNK和c-Jun的磷酸化水平来评估JNK信号通路的激活。
U87胶质瘤细胞中GOLPH3的下调显著增强了细胞凋亡，这通过裂解的半胱天冬酶-3水平升高和更高的凋亡率得到证明。此外，GOLPH3敲低导致JNK信号通路的激活，表现为JNK和c-Jun磷酸化水平升高。此外，GOLPH3表达的抑制抑制了肿瘤生长并增加了肿瘤微环境中的细胞凋亡。
这些发现表明，GOLPH3可能通过JNK信号通路在调节恶性胶质瘤细胞凋亡中起关键作用。因此，GOLPH3可能是胶质瘤治疗的一个有前景的治疗靶点。
