RETRACTED ARTICLE: BRD9 inhibition promotes PUMA-dependent apoptosis and augments the effect of imatinib in gastrointestinal stromal tumors
Abstract Gastrointestinal stromal tumors (GISTs) are primarily characterized by activating mutations of tyrosine kinase or platelet-derived growth factor receptor alpha. Although the revolutionary therapeutic outcomes of imatinib are well known, the long-term benefits of imatinib are still unclear....
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-10-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-04186-6 |
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| _version_ | 1850136973555007488 |
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| author | Jianfeng Mu Xuezeng Sun Zhipeng Zhao Hao Sun Pengda Sun |
| author_facet | Jianfeng Mu Xuezeng Sun Zhipeng Zhao Hao Sun Pengda Sun |
| author_sort | Jianfeng Mu |
| collection | DOAJ |
| description | Abstract Gastrointestinal stromal tumors (GISTs) are primarily characterized by activating mutations of tyrosine kinase or platelet-derived growth factor receptor alpha. Although the revolutionary therapeutic outcomes of imatinib are well known, the long-term benefits of imatinib are still unclear. The effects of BRD9, a recently identified subunit of noncanonical BAF complex (ncBAF) chromatin remodeling complexes, in GISTs are not clear. In the current study, we evaluated the functional role of BRD9 in GIST progression. Our findings demonstrated that the expression of BRD9 was upregulated in GIST tissues. The downregulation or inhibition of BRD9 could significantly reduce cellular proliferation, and facilitates apoptosis in GISTs. BRD9 inhibition could promote PUMA-dependent apoptosis in GISTs and enhance imatinib activity in vitro and in vivo. BRD9 inhibition synergizes with imatinib in GISTs by inducing PUMA upregulation. Mechanism study revealed that BRD9 inhibition promotes PUMA induction via the TUFT1/AKT/GSK-3β/p65 axis. Furthermore, imatinib also upregulates PUMA by targeting AKT/GSK-3β/p65 axis. In conclusion, our results indicated that BRD9 plays a key role in the progression of GISTs. Inhibition of BRD9 is a novel therapeutic strategy in GISTs treated alone or in combination with imatinib. |
| format | Article |
| id | doaj-art-3e6892f00a31451a8ee1fb65fc6dffd7 |
| institution | OA Journals |
| issn | 2041-4889 |
| language | English |
| publishDate | 2021-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-3e6892f00a31451a8ee1fb65fc6dffd72025-08-20T02:30:59ZengNature Publishing GroupCell Death and Disease2041-48892021-10-01121111010.1038/s41419-021-04186-6RETRACTED ARTICLE: BRD9 inhibition promotes PUMA-dependent apoptosis and augments the effect of imatinib in gastrointestinal stromal tumorsJianfeng Mu0Xuezeng Sun1Zhipeng Zhao2Hao Sun3Pengda Sun4Department of Gastric and Colorectal Surgery, The First Hospital of Jilin UniversityDepartment of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin UniversityDepartment of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin UniversityDepartment of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin UniversityDepartment of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin UniversityAbstract Gastrointestinal stromal tumors (GISTs) are primarily characterized by activating mutations of tyrosine kinase or platelet-derived growth factor receptor alpha. Although the revolutionary therapeutic outcomes of imatinib are well known, the long-term benefits of imatinib are still unclear. The effects of BRD9, a recently identified subunit of noncanonical BAF complex (ncBAF) chromatin remodeling complexes, in GISTs are not clear. In the current study, we evaluated the functional role of BRD9 in GIST progression. Our findings demonstrated that the expression of BRD9 was upregulated in GIST tissues. The downregulation or inhibition of BRD9 could significantly reduce cellular proliferation, and facilitates apoptosis in GISTs. BRD9 inhibition could promote PUMA-dependent apoptosis in GISTs and enhance imatinib activity in vitro and in vivo. BRD9 inhibition synergizes with imatinib in GISTs by inducing PUMA upregulation. Mechanism study revealed that BRD9 inhibition promotes PUMA induction via the TUFT1/AKT/GSK-3β/p65 axis. Furthermore, imatinib also upregulates PUMA by targeting AKT/GSK-3β/p65 axis. In conclusion, our results indicated that BRD9 plays a key role in the progression of GISTs. Inhibition of BRD9 is a novel therapeutic strategy in GISTs treated alone or in combination with imatinib.https://doi.org/10.1038/s41419-021-04186-6 |
| spellingShingle | Jianfeng Mu Xuezeng Sun Zhipeng Zhao Hao Sun Pengda Sun RETRACTED ARTICLE: BRD9 inhibition promotes PUMA-dependent apoptosis and augments the effect of imatinib in gastrointestinal stromal tumors Cell Death and Disease |
| title | RETRACTED ARTICLE: BRD9 inhibition promotes PUMA-dependent apoptosis and augments the effect of imatinib in gastrointestinal stromal tumors |
| title_full | RETRACTED ARTICLE: BRD9 inhibition promotes PUMA-dependent apoptosis and augments the effect of imatinib in gastrointestinal stromal tumors |
| title_fullStr | RETRACTED ARTICLE: BRD9 inhibition promotes PUMA-dependent apoptosis and augments the effect of imatinib in gastrointestinal stromal tumors |
| title_full_unstemmed | RETRACTED ARTICLE: BRD9 inhibition promotes PUMA-dependent apoptosis and augments the effect of imatinib in gastrointestinal stromal tumors |
| title_short | RETRACTED ARTICLE: BRD9 inhibition promotes PUMA-dependent apoptosis and augments the effect of imatinib in gastrointestinal stromal tumors |
| title_sort | retracted article brd9 inhibition promotes puma dependent apoptosis and augments the effect of imatinib in gastrointestinal stromal tumors |
| url | https://doi.org/10.1038/s41419-021-04186-6 |
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