TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 protein
Abstract Background The tripartite motif (TRIM) family of proteins plays a key role in the developmental growth and therapeutic resistance of many tumors. However, the regulatory mechanisms and biological functions of TRIM proteins in human glioblastoma (GBM) are not yet fully understood. In this st...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-022-02534-8 |
| _version_ | 1811203662668627968 |
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| author | Xu Yang Yan Zhang Zhiwei Xue Yaotian Hu Wenjing Zhou Zhiyi Xue Xuemeng Liu Guowei Liu Wenjie Li Xiaofei Liu Xingang Li Mingzhi Han Jian Wang |
| author_facet | Xu Yang Yan Zhang Zhiwei Xue Yaotian Hu Wenjing Zhou Zhiyi Xue Xuemeng Liu Guowei Liu Wenjie Li Xiaofei Liu Xingang Li Mingzhi Han Jian Wang |
| author_sort | Xu Yang |
| collection | DOAJ |
| description | Abstract Background The tripartite motif (TRIM) family of proteins plays a key role in the developmental growth and therapeutic resistance of many tumors. However, the regulatory mechanisms and biological functions of TRIM proteins in human glioblastoma (GBM) are not yet fully understood. In this study, we focused on TRIM56, which emerged as the most differentially expressed TRIM family member with increased expression in GBM. Methods Western blot, real-time quantitative PCR (qRT-PCR), immunofluorescence (IF) and immunohistochemistry (IHC) were used to study the expression levels of TRIM56 and cIAP1 in GBM cell lines. Co-immunoprecipitation (co-IP) was used to explore the specific binding between target proteins and TRIM56. A xenograft animal model was used to verify the tumor promoting effect of TRIM56 on glioma in vivo. Results We observed elevated expression of TRIM56 in malignant gliomas and revealed that TRIM56 promoted glioma progression in vitro and in a GBM xenograft model in nude mice. Analysis of the Human Ubiquitin Array and co-IPs showed that cIAP1 is a protein downstream of TRIM56. TRIM56 deubiquitinated cIAP1, mainly through the zinc finger domain (amino acids 21–205) of TRIM56, thereby reducing the degradation of cIAP1 and thus increasing its expression. TRIM56 also showed prognostic significance in overall survival of glioma patients. Conclusions TRIM56-regulated post-translational modifications may contribute to glioma development through stabilization of cIAP1. Furthermore, TRIM56 may serve as a novel prognostic indicator and therapeutic molecular target for GBM. |
| first_indexed | 2024-04-12T03:00:11Z |
| format | Article |
| id | doaj.art-fd8b62aabe874c32987cbe945dbb348b |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-12T03:00:11Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-fd8b62aabe874c32987cbe945dbb348b2022-12-22T03:50:42ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662022-12-0141111810.1186/s13046-022-02534-8TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 proteinXu Yang0Yan Zhang1Zhiwei Xue2Yaotian Hu3Wenjing Zhou4Zhiyi Xue5Xuemeng Liu6Guowei Liu7Wenjie Li8Xiaofei Liu9Xingang Li10Mingzhi Han11Jian Wang12Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Blood Transfusion, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityAbstract Background The tripartite motif (TRIM) family of proteins plays a key role in the developmental growth and therapeutic resistance of many tumors. However, the regulatory mechanisms and biological functions of TRIM proteins in human glioblastoma (GBM) are not yet fully understood. In this study, we focused on TRIM56, which emerged as the most differentially expressed TRIM family member with increased expression in GBM. Methods Western blot, real-time quantitative PCR (qRT-PCR), immunofluorescence (IF) and immunohistochemistry (IHC) were used to study the expression levels of TRIM56 and cIAP1 in GBM cell lines. Co-immunoprecipitation (co-IP) was used to explore the specific binding between target proteins and TRIM56. A xenograft animal model was used to verify the tumor promoting effect of TRIM56 on glioma in vivo. Results We observed elevated expression of TRIM56 in malignant gliomas and revealed that TRIM56 promoted glioma progression in vitro and in a GBM xenograft model in nude mice. Analysis of the Human Ubiquitin Array and co-IPs showed that cIAP1 is a protein downstream of TRIM56. TRIM56 deubiquitinated cIAP1, mainly through the zinc finger domain (amino acids 21–205) of TRIM56, thereby reducing the degradation of cIAP1 and thus increasing its expression. TRIM56 also showed prognostic significance in overall survival of glioma patients. Conclusions TRIM56-regulated post-translational modifications may contribute to glioma development through stabilization of cIAP1. Furthermore, TRIM56 may serve as a novel prognostic indicator and therapeutic molecular target for GBM.https://doi.org/10.1186/s13046-022-02534-8GliomaDeubiquitylationTRIM56cIAP1 |
| spellingShingle | Xu Yang Yan Zhang Zhiwei Xue Yaotian Hu Wenjing Zhou Zhiyi Xue Xuemeng Liu Guowei Liu Wenjie Li Xiaofei Liu Xingang Li Mingzhi Han Jian Wang TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 protein Journal of Experimental & Clinical Cancer Research Glioma Deubiquitylation TRIM56 cIAP1 |
| title | TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 protein |
| title_full | TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 protein |
| title_fullStr | TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 protein |
| title_full_unstemmed | TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 protein |
| title_short | TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 protein |
| title_sort | trim56 promotes malignant progression of glioblastoma by stabilizing ciap1 protein |
| topic | Glioma Deubiquitylation TRIM56 cIAP1 |
| url | https://doi.org/10.1186/s13046-022-02534-8 |
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