دورية أكاديمية
Genome-wide enhancer RNA profiling adds molecular links between genetic variation and human cancers.
| العنوان: | Genome-wide enhancer RNA profiling adds molecular links between genetic variation and human cancers. |
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| المؤلفون: | Cai YM; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China.; Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China.; Department of Cancer Epidemiology, Henan Engineering Research Center of Cancer Prevention and Control, Henan International Joint Laboratory of Cancer Prevention, the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China., Lu ZQ; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China.; Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China.; Department of Cancer Epidemiology, Henan Engineering Research Center of Cancer Prevention and Control, Henan International Joint Laboratory of Cancer Prevention, the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China., Li B; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China.; Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China.; Department of Cancer Epidemiology, Henan Engineering Research Center of Cancer Prevention and Control, Henan International Joint Laboratory of Cancer Prevention, the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China., Huang JY; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China., Zhang M; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China., Chen C; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China., Fan LY; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China., Ma QY; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China., He CY; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China., Chen SN; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China., Jiang Y; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China., Li YM; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China., Ning CB; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China., Zhang FW; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China., Wang WZ; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China., Liu YZ; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China., Zhang H; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China., Jin M; Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China., Wang XY; Department of Cancer Epidemiology, Henan Engineering Research Center of Cancer Prevention and Control, Henan International Joint Laboratory of Cancer Prevention, the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China., Han JX; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China., Xiong Z; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China., Cai M; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China., Huang CQ; Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China., Yang XJ; Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China., Zhu X; Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China., Zhu Y; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China., Miao XP; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China. xpmiao@whu.edu.cn.; Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China. xpmiao@whu.edu.cn.; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. xpmiao@whu.edu.cn.; Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China. xpmiao@whu.edu.cn., Zhang SK; Department of Cancer Epidemiology, Henan Engineering Research Center of Cancer Prevention and Control, Henan International Joint Laboratory of Cancer Prevention, the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China. shaokaizhang@126.com., Wei YC; Department of Gastrointestinal Oncology, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. weiyongchang@whu.edu.cn., Tian JB; Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China. tianjb@whu.edu.cn.; Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China. tianjb@whu.edu.cn.; Department of Cancer Epidemiology, Henan Engineering Research Center of Cancer Prevention and Control, Henan International Joint Laboratory of Cancer Prevention, the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China. tianjb@whu.edu.cn. |
| المصدر: | Military Medical Research [Mil Med Res] 2024 Jun 11; Vol. 11 (1), pp. 36. Date of Electronic Publication: 2024 Jun 11. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101643181 Publication Model: Electronic Cited Medium: Internet ISSN: 2054-9369 (Electronic) Linking ISSN: 20549369 NLM ISO Abbreviation: Mil Med Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [London] : BioMed Central, [2014]- |
| مواضيع طبية MeSH: | Quantitative Trait Loci* , Enhancer Elements, Genetic*/genetics , Neoplasms*/genetics, Humans ; Genetic Variation/genetics ; Genome-Wide Association Study/methods ; Colorectal Neoplasms/genetics ; Case-Control Studies ; RNA/genetics ; China ; Enhancer RNAs |
| مستخلص: | Background: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. Methods: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. Results: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88-0.95, P = 2.92 × 10 -7 ) and Europe (OR = 0.92, 95%CI 0.88-0.95, P = 4.61 × 10 -6 ). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. Conclusion: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers. (© 2024. The Author(s).) |
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| معلومات مُعتمدة: | NSFC-82103929 The Program of National Natural Science Foundation of China; NSFC-82273713 The Program of National Natural Science Foundation of China; 2022QNRC001 Young Elite Scientists Sponsorship Program by CAST; NSFC-81925032 Distinguished Young Scholars of China; NSFC-82130098 Key Program of National Natural Science Foundation of China; 2042022rc0026 Fundamental Research Funds for the Central Universities; 2042023kf1005 Fundamental Research Funds for the Central Universities; WHU:2042022kf1205 Fundamental Research Funds for the Central Universities; WHU: 2042022kf1031 Fundamental Research Funds for the Central Universities; whkxjsj011 Knowledge Innovation Program of Wuhan; 2023020201010073 Knowledge Innovation Program of Wuhan; NSFC-82003547 Youth Program of National Natural Science Foundation of China; WJ2023M045 Program of Health Commission of Hubei Province; NSFC-82322058 National Science Fund for Excellent Young Scholars; 2023AFA046 National Science Fund for Distinguished Young Scholars of Hubei Province of China; znpy2019060 Science and Technology Innovation Seed Fund of Zhongnan Hospital of Wuhan University |
| فهرسة مساهمة: | Keywords: ENSR00000155786; SENP7; Enhancer RNA; Genome-wide association study (GWAS); eRNA quantitative trait loci (eRNAQTLs) |
| المشرفين على المادة: | 63231-63-0 (RNA) 0 (Enhancer RNAs) |
| تواريخ الأحداث: | Date Created: 20240611 Date Completed: 20240612 Latest Revision: 20240613 |
| رمز التحديث: | 20240613 |
| مُعرف محوري في PubMed: | PMC11165858 |
| DOI: | 10.1186/s40779-024-00539-2 |
| PMID: | 38863031 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 2054-9369 |
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| DOI: | 10.1186/s40779-024-00539-2 |