Bivalent activity of super-enhancer RNA LINC02454 controls 3D chromatin structure and regulates glioma sensitivity to temozolomide
Abstract Glioma cell sensitivity to temozolomide (TMZ) is critical for effective treatment and correlates with patient survival, although mechanisms underlying this activity are unclear. Here, we reveal a new mechanism used by glioma cells to modulate TMZ sensitivity via regulation of SORBS2 and DDR...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2024-01-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-06392-w |
| _version_ | 1797362836639318016 |
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| author | Tengfei Shi Dianhao Guo Yaoqiang Zheng Wenbin Wang Jinfang Bi Anshun He Sibo Fan Guangsong Su Xueyuan Zhao Zhenhao Zhao Yingjie Song Shupeng Sun Peng Li Zhongfang Zhao Jiandang Shi Wange Lu Lei Zhang |
| author_facet | Tengfei Shi Dianhao Guo Yaoqiang Zheng Wenbin Wang Jinfang Bi Anshun He Sibo Fan Guangsong Su Xueyuan Zhao Zhenhao Zhao Yingjie Song Shupeng Sun Peng Li Zhongfang Zhao Jiandang Shi Wange Lu Lei Zhang |
| author_sort | Tengfei Shi |
| collection | DOAJ |
| description | Abstract Glioma cell sensitivity to temozolomide (TMZ) is critical for effective treatment and correlates with patient survival, although mechanisms underlying this activity are unclear. Here, we reveal a new mechanism used by glioma cells to modulate TMZ sensitivity via regulation of SORBS2 and DDR1 genes by super-enhancer RNA LINC02454. We report that LINC02454 activity increases glioma cell TMZ sensitivity by maintaining long-range chromatin interactions between SORBS2 and the LINC02454 enhancer. By contrast, LINC02454 activity also decreased glioma cell TMZ sensitivity by promoting DDR1 expression. Our study suggests a bivalent function for super-enhancer RNA LINC02454 in regulating glioma cell sensitivity to TMZ. |
| first_indexed | 2024-03-08T16:12:10Z |
| format | Article |
| id | doaj.art-3968c6b5c3f8445ea4776a806595d274 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-08T16:12:10Z |
| publishDate | 2024-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-3968c6b5c3f8445ea4776a806595d2742024-01-07T12:49:30ZengNature Publishing GroupCell Death and Disease2041-48892024-01-0115111310.1038/s41419-023-06392-wBivalent activity of super-enhancer RNA LINC02454 controls 3D chromatin structure and regulates glioma sensitivity to temozolomideTengfei Shi0Dianhao Guo1Yaoqiang Zheng2Wenbin Wang3Jinfang Bi4Anshun He5Sibo Fan6Guangsong Su7Xueyuan Zhao8Zhenhao Zhao9Yingjie Song10Shupeng Sun11Peng Li12Zhongfang Zhao13Jiandang Shi14Wange Lu15Lei Zhang16State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityDepartment of Molecular Biology and Biochemistry, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical SciencesState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityInstitute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen UniversityState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityInstitute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen UniversityState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityDepartment of Neurosurgery, Tianjin Huanhu Hospital, School of Medicine, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityAbstract Glioma cell sensitivity to temozolomide (TMZ) is critical for effective treatment and correlates with patient survival, although mechanisms underlying this activity are unclear. Here, we reveal a new mechanism used by glioma cells to modulate TMZ sensitivity via regulation of SORBS2 and DDR1 genes by super-enhancer RNA LINC02454. We report that LINC02454 activity increases glioma cell TMZ sensitivity by maintaining long-range chromatin interactions between SORBS2 and the LINC02454 enhancer. By contrast, LINC02454 activity also decreased glioma cell TMZ sensitivity by promoting DDR1 expression. Our study suggests a bivalent function for super-enhancer RNA LINC02454 in regulating glioma cell sensitivity to TMZ.https://doi.org/10.1038/s41419-023-06392-w |
| spellingShingle | Tengfei Shi Dianhao Guo Yaoqiang Zheng Wenbin Wang Jinfang Bi Anshun He Sibo Fan Guangsong Su Xueyuan Zhao Zhenhao Zhao Yingjie Song Shupeng Sun Peng Li Zhongfang Zhao Jiandang Shi Wange Lu Lei Zhang Bivalent activity of super-enhancer RNA LINC02454 controls 3D chromatin structure and regulates glioma sensitivity to temozolomide Cell Death and Disease |
| title | Bivalent activity of super-enhancer RNA LINC02454 controls 3D chromatin structure and regulates glioma sensitivity to temozolomide |
| title_full | Bivalent activity of super-enhancer RNA LINC02454 controls 3D chromatin structure and regulates glioma sensitivity to temozolomide |
| title_fullStr | Bivalent activity of super-enhancer RNA LINC02454 controls 3D chromatin structure and regulates glioma sensitivity to temozolomide |
| title_full_unstemmed | Bivalent activity of super-enhancer RNA LINC02454 controls 3D chromatin structure and regulates glioma sensitivity to temozolomide |
| title_short | Bivalent activity of super-enhancer RNA LINC02454 controls 3D chromatin structure and regulates glioma sensitivity to temozolomide |
| title_sort | bivalent activity of super enhancer rna linc02454 controls 3d chromatin structure and regulates glioma sensitivity to temozolomide |
| url | https://doi.org/10.1038/s41419-023-06392-w |
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