GOLPH3 inhibits glioma cell apoptosis through the JNK signaling pathway
BackgroundGlioma, 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...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2025.1518573/full |
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| author | Shao Xie Shao Xie Jiahai Ding Zhaohao Wang Hengliang Shi Zheng-Quan Yu |
| author_facet | Shao Xie Shao Xie Jiahai Ding Zhaohao Wang Hengliang Shi Zheng-Quan Yu |
| author_sort | Shao Xie |
| collection | DOAJ |
| description | BackgroundGlioma, 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.MethodsTo elucidate the function of GOLPH3, U87 glioma cells were transfected with GOLPH3-specific small interfering RNA (siRNA) to suppress its expression. An in vivo 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.ResultsDownregulation 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. In vivo, suppression of GOLPH3 expression inhibited tumor growth and increased apoptosis within the tumor microenvironment.ConclusionThese 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. |
| format | Article |
| id | doaj-art-a3a9a245878a434884b79575d9245d30 |
| institution | Kabale University |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj-art-a3a9a245878a434884b79575d9245d302025-01-29T06:46:20ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-01-011610.3389/fgene.2025.15185731518573GOLPH3 inhibits glioma cell apoptosis through the JNK signaling pathwayShao Xie0Shao Xie1Jiahai Ding2Zhaohao Wang3Hengliang Shi4Zheng-Quan Yu5Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, ChinaDepartment of Neurosurgery, Yantaishan Hospital Affiliated to Binzhou Medical University, Yantai, ChinaCentral Laboratory, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaBackgroundGlioma, 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.MethodsTo elucidate the function of GOLPH3, U87 glioma cells were transfected with GOLPH3-specific small interfering RNA (siRNA) to suppress its expression. An in vivo 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.ResultsDownregulation 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. In vivo, suppression of GOLPH3 expression inhibited tumor growth and increased apoptosis within the tumor microenvironment.ConclusionThese 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.https://www.frontiersin.org/articles/10.3389/fgene.2025.1518573/fullgliomaGOLPH3JNKapoptosistherapeutic target |
| spellingShingle | Shao Xie Shao Xie Jiahai Ding Zhaohao Wang Hengliang Shi Zheng-Quan Yu GOLPH3 inhibits glioma cell apoptosis through the JNK signaling pathway Frontiers in Genetics glioma GOLPH3 JNK apoptosis therapeutic target |
| title | GOLPH3 inhibits glioma cell apoptosis through the JNK signaling pathway |
| title_full | GOLPH3 inhibits glioma cell apoptosis through the JNK signaling pathway |
| title_fullStr | GOLPH3 inhibits glioma cell apoptosis through the JNK signaling pathway |
| title_full_unstemmed | GOLPH3 inhibits glioma cell apoptosis through the JNK signaling pathway |
| title_short | GOLPH3 inhibits glioma cell apoptosis through the JNK signaling pathway |
| title_sort | golph3 inhibits glioma cell apoptosis through the jnk signaling pathway |
| topic | glioma GOLPH3 JNK apoptosis therapeutic target |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1518573/full |
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