A p53/LINC00324 positive feedback loop suppresses tumor growth by counteracting SET-mediated transcriptional repression
Summary: The p53 tumor suppressor exerts antitumor functions through its ability to regulate the transcription of its downstream targets. Long noncoding RNAs (lncRNAs) act as oncogenes or tumor suppressors implicated in tumorigenesis and tumor progression. Here, we identify the lncRNA LINC00324 (lon...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723008446 |
| _version_ | 1797731127706779648 |
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| author | Ling Zhang Jun Zhang Xiaofeng Xuan Di Wu Jianfeng Yu Peizhen Wang Xiaomei Yang Jieru Zhang Wenjuan Gan Mengfan He Xiao-Min Liu Jun Zhou Donglai Wang Wei Gu Dawei Li |
| author_facet | Ling Zhang Jun Zhang Xiaofeng Xuan Di Wu Jianfeng Yu Peizhen Wang Xiaomei Yang Jieru Zhang Wenjuan Gan Mengfan He Xiao-Min Liu Jun Zhou Donglai Wang Wei Gu Dawei Li |
| author_sort | Ling Zhang |
| collection | DOAJ |
| description | Summary: The p53 tumor suppressor exerts antitumor functions through its ability to regulate the transcription of its downstream targets. Long noncoding RNAs (lncRNAs) act as oncogenes or tumor suppressors implicated in tumorigenesis and tumor progression. Here, we identify the lncRNA LINC00324 (long intergenic noncoding RNA 00324) as a direct p53 transcriptional target. Knockdown of LINC00324 expression promotes tumor growth by reducing p53 transcriptional activity, whereas ectopic LINC00324 expression demonstrates a reverse effect. Notably, LINC00324 is present in the endogenous p53 complex in tumor cells and directly binds to the C-terminal domain of p53 in vitro. Mechanistically, LINC00324 enables p53 transactivation by competitively disrupting the p53-SET interaction, resulting in an increase of p300/CBP-mediated H3K18 and H3K27 acetylation on the p53 target promoters. Lower LINC00324 expression is associated with more aggressive disease status and predicts worse overall survival of patients with cancer. Our study identifies a p53/LINC00324 positive feedback loop that suppresses tumor growth by counteracting SET-mediated transcriptional repression. |
| first_indexed | 2024-03-12T11:54:17Z |
| format | Article |
| id | doaj.art-fee8d5f488d841faaffee229cfe9eed1 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-12T11:54:17Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-fee8d5f488d841faaffee229cfe9eed12023-08-31T05:01:47ZengElsevierCell Reports2211-12472023-08-01428112833A p53/LINC00324 positive feedback loop suppresses tumor growth by counteracting SET-mediated transcriptional repressionLing Zhang0Jun Zhang1Xiaofeng Xuan2Di Wu3Jianfeng Yu4Peizhen Wang5Xiaomei Yang6Jieru Zhang7Wenjuan Gan8Mengfan He9Xiao-Min Liu10Jun Zhou11Donglai Wang12Wei Gu13Dawei Li14Center for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, 68 Jiyang West Road, Suzhou 215600, ChinaSchool of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, ChinaDepartment of Respiratory & Critical Care Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, 68 Jiyang West Road, Suzhou 215600, ChinaCenter for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, 68 Jiyang West Road, Suzhou 215600, ChinaDepartment of Life Science and Technology, Changshu Institute of Technology, 99 South Third Ring Road, Suzhou 215500, ChinaCenter for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, 68 Jiyang West Road, Suzhou 215600, ChinaDepartment of Emergency, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, 68 Jiyang West Road, Suzhou 215600, ChinaDepartment of Respiratory & Critical Care Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, 68 Jiyang West Road, Suzhou 215600, ChinaDepartment of Pathology, Dushu Lake Hospital Affiliated to Soochow University, 9 Chongwen Road, Suzhou 215300, ChinaCenter for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, 68 Jiyang West Road, Suzhou 215600, ChinaSchool of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, ChinaSchool of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, ChinaState Key Laboratory of Medical Molecular Biology and Department of Medical Genetics, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, ChinaInstitute for Cancer Genetics, and Department of Pathology and Cell Biology, and Herbert Irving Comprehensive Cancer Center, College of Physicians & Surgeons, Columbia University, 1130 St. Nicholas Avenue, New York, NY 10032, USACenter for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, 68 Jiyang West Road, Suzhou 215600, China; Corresponding authorSummary: The p53 tumor suppressor exerts antitumor functions through its ability to regulate the transcription of its downstream targets. Long noncoding RNAs (lncRNAs) act as oncogenes or tumor suppressors implicated in tumorigenesis and tumor progression. Here, we identify the lncRNA LINC00324 (long intergenic noncoding RNA 00324) as a direct p53 transcriptional target. Knockdown of LINC00324 expression promotes tumor growth by reducing p53 transcriptional activity, whereas ectopic LINC00324 expression demonstrates a reverse effect. Notably, LINC00324 is present in the endogenous p53 complex in tumor cells and directly binds to the C-terminal domain of p53 in vitro. Mechanistically, LINC00324 enables p53 transactivation by competitively disrupting the p53-SET interaction, resulting in an increase of p300/CBP-mediated H3K18 and H3K27 acetylation on the p53 target promoters. Lower LINC00324 expression is associated with more aggressive disease status and predicts worse overall survival of patients with cancer. Our study identifies a p53/LINC00324 positive feedback loop that suppresses tumor growth by counteracting SET-mediated transcriptional repression.http://www.sciencedirect.com/science/article/pii/S2211124723008446CP: Cancer |
| spellingShingle | Ling Zhang Jun Zhang Xiaofeng Xuan Di Wu Jianfeng Yu Peizhen Wang Xiaomei Yang Jieru Zhang Wenjuan Gan Mengfan He Xiao-Min Liu Jun Zhou Donglai Wang Wei Gu Dawei Li A p53/LINC00324 positive feedback loop suppresses tumor growth by counteracting SET-mediated transcriptional repression Cell Reports CP: Cancer |
| title | A p53/LINC00324 positive feedback loop suppresses tumor growth by counteracting SET-mediated transcriptional repression |
| title_full | A p53/LINC00324 positive feedback loop suppresses tumor growth by counteracting SET-mediated transcriptional repression |
| title_fullStr | A p53/LINC00324 positive feedback loop suppresses tumor growth by counteracting SET-mediated transcriptional repression |
| title_full_unstemmed | A p53/LINC00324 positive feedback loop suppresses tumor growth by counteracting SET-mediated transcriptional repression |
| title_short | A p53/LINC00324 positive feedback loop suppresses tumor growth by counteracting SET-mediated transcriptional repression |
| title_sort | p53 linc00324 positive feedback loop suppresses tumor growth by counteracting set mediated transcriptional repression |
| topic | CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723008446 |
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