Palmitoyl transferases act as potential regulators of tumor-infiltrating immune cells and glioma progression
High immune-cell infiltration in glioblastomas (GBMs) leads to immunotherapy resistance. Emerging evidence has shown that zinc finger Asp-His-His-Cyc-type (ZDHHC) palmitoyl transferases participate in regulating tumor progression and the immune microenvironment. In the present study, a large cohort...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S216225312200107X |
| _version_ | 1811257591475470336 |
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| author | Feng Tang Chao Yang Feng-Ping Li Dong-Hu Yu Zhi-Yong Pan Ze-Fen Wang Zhi-Qiang Li |
| author_facet | Feng Tang Chao Yang Feng-Ping Li Dong-Hu Yu Zhi-Yong Pan Ze-Fen Wang Zhi-Qiang Li |
| author_sort | Feng Tang |
| collection | DOAJ |
| description | High immune-cell infiltration in glioblastomas (GBMs) leads to immunotherapy resistance. Emerging evidence has shown that zinc finger Asp-His-His-Cyc-type (ZDHHC) palmitoyl transferases participate in regulating tumor progression and the immune microenvironment. In the present study, a large cohort of patients with gliomas from The Cancer Genome Atlas (TCGA) and Rembrandt databases was included to perform omics analysis of ZDHHCs in gliomas. CCK-8, flow cytometry, quantitative real-time PCR, western blotting, and transwell assays were performed to determine the effects of ZDHHC inhibition on glioma cells and microglia. We found that five (ZDHHC11, ZDHHC12, ZDHHC15, ZDHHC22, and ZDHHC23) out of 23 ZDHHCs were aberrantly expressed in gliomas and might play their roles through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. Further results indicated that inhibition of ZDHHCs with 2-bromopalmitate (2-BP) suppressed glioma-cell viability and autophagy, as well as promoted apoptosis. Targeting ZDHHCs also promoted the sensitivity of glioma cells to temozolomide (TMZ) chemotherapy. In addition, the inhibition of ZDHHCs weakened the migratory ability of microglia induced by glioma cells in vitro and in vivo. Taken together, our findings suggest that the inhibition of ZDHHCs suppresses glioma-cell viability and microglial infiltration. Targeting ZDHHCs may be promising for glioma treatments. |
| first_indexed | 2024-04-12T17:59:49Z |
| format | Article |
| id | doaj.art-eaa561b5a51649df955d19c257b7fb39 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-04-12T17:59:49Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-eaa561b5a51649df955d19c257b7fb392022-12-22T03:22:12ZengElsevierMolecular Therapy: Nucleic Acids2162-25312022-06-0128716731Palmitoyl transferases act as potential regulators of tumor-infiltrating immune cells and glioma progressionFeng Tang0Chao Yang1Feng-Ping Li2Dong-Hu Yu3Zhi-Yong Pan4Ze-Fen Wang5Zhi-Qiang Li6Brain Glioma Center & Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, ChinaBrain Glioma Center & Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, ChinaBrain Glioma Center & Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, ChinaBrain Glioma Center & Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, ChinaBrain Glioma Center & Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of Physiology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei, China; Corresponding author Ze-Fen Wang, Department of Physiology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei, China.Brain Glioma Center & Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China; Corresponding author Zhi-Qiang Li, Brain Glioma Center & Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.High immune-cell infiltration in glioblastomas (GBMs) leads to immunotherapy resistance. Emerging evidence has shown that zinc finger Asp-His-His-Cyc-type (ZDHHC) palmitoyl transferases participate in regulating tumor progression and the immune microenvironment. In the present study, a large cohort of patients with gliomas from The Cancer Genome Atlas (TCGA) and Rembrandt databases was included to perform omics analysis of ZDHHCs in gliomas. CCK-8, flow cytometry, quantitative real-time PCR, western blotting, and transwell assays were performed to determine the effects of ZDHHC inhibition on glioma cells and microglia. We found that five (ZDHHC11, ZDHHC12, ZDHHC15, ZDHHC22, and ZDHHC23) out of 23 ZDHHCs were aberrantly expressed in gliomas and might play their roles through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. Further results indicated that inhibition of ZDHHCs with 2-bromopalmitate (2-BP) suppressed glioma-cell viability and autophagy, as well as promoted apoptosis. Targeting ZDHHCs also promoted the sensitivity of glioma cells to temozolomide (TMZ) chemotherapy. In addition, the inhibition of ZDHHCs weakened the migratory ability of microglia induced by glioma cells in vitro and in vivo. Taken together, our findings suggest that the inhibition of ZDHHCs suppresses glioma-cell viability and microglial infiltration. Targeting ZDHHCs may be promising for glioma treatments.http://www.sciencedirect.com/science/article/pii/S216225312200107XMT: BioinformaticsZDHHCsimmune-cell infiltrationgliomaspost-translational modificationsignaling pathway |
| spellingShingle | Feng Tang Chao Yang Feng-Ping Li Dong-Hu Yu Zhi-Yong Pan Ze-Fen Wang Zhi-Qiang Li Palmitoyl transferases act as potential regulators of tumor-infiltrating immune cells and glioma progression Molecular Therapy: Nucleic Acids MT: Bioinformatics ZDHHCs immune-cell infiltration gliomas post-translational modification signaling pathway |
| title | Palmitoyl transferases act as potential regulators of tumor-infiltrating immune cells and glioma progression |
| title_full | Palmitoyl transferases act as potential regulators of tumor-infiltrating immune cells and glioma progression |
| title_fullStr | Palmitoyl transferases act as potential regulators of tumor-infiltrating immune cells and glioma progression |
| title_full_unstemmed | Palmitoyl transferases act as potential regulators of tumor-infiltrating immune cells and glioma progression |
| title_short | Palmitoyl transferases act as potential regulators of tumor-infiltrating immune cells and glioma progression |
| title_sort | palmitoyl transferases act as potential regulators of tumor infiltrating immune cells and glioma progression |
| topic | MT: Bioinformatics ZDHHCs immune-cell infiltration gliomas post-translational modification signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S216225312200107X |
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