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An enhancer variant at 16q22.1 predisposes to hepatocellular carcinoma via regulating PRMT7 expression.
Shen, Ting; Ni, Ting; Chen, Jiaxuan; Chen, Haitao; Ma, Xiaopin; Cao, Guangwen; Wu, Tianzhi; Xie, Haisheng; Zhou, Bin; Wei, Gang; Saiyin, Hexige; Shen, Suqin; Yu, Peng; Xiao, Qianyi; Liu, Hui; Gao, Yuzheng; Long, Xidai; Yin, Jianhua; Guo, Yanfang; Wu, Jiaxue; Wei, Gong-Hong; Hou, Jinlin; Jiang, De-Ke.
Afiliación
  • Shen T; State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China.
  • Ni T; School of Life Sciences, Central South University, 510006, Changsha, China.
  • Chen J; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, Human Phenome Institute, School of Life Sciences, Fudan University, 200438, Shanghai, China.
  • Chen H; State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China.
  • Ma X; State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China.
  • Cao G; School of Public Health (Shenzhen), Sun Yat-sen University, 528406, Shenzhen, China.
  • Wu T; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, Human Phenome Institute, School of Life Sciences, Fudan University, 200438, Shanghai, China.
  • Xie H; Department of Epidemiology, Naval Medical University, 200433, Shanghai, China.
  • Zhou B; Institute of Bioinformatics, School of Basic Medical Science, Southern Medical University, 510515, Guangzhou, China.
  • Wei G; State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China.
  • Saiyin H; State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China.
  • Shen S; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, Human Phenome Institute, School of Life Sciences, Fudan University, 200438, Shanghai, China.
  • Yu P; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, Human Phenome Institute, School of Life Sciences, Fudan University, 200438, Shanghai, China.
  • Xiao Q; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, Human Phenome Institute, School of Life Sciences, Fudan University, 200438, Shanghai, China.
  • Liu H; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, Human Phenome Institute, School of Life Sciences, Fudan University, 200438, Shanghai, China.
  • Gao Y; School of Public Health, Fudan University, 200032, Shanghai, China.
  • Long X; School of Basic Medical Sciences; The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's hospital, Guangzhou Medical University, 510182, Guangzhou, China.
  • Yin J; Department of Forensic Medicine, Medical College of Soochow University, 215123, Suzhou, Jiangsu Province, China.
  • Guo Y; Department of Pathology, Youjiang Medical College for Nationalities, 533000, Baise, Guangxi Province, China.
  • Wu J; Department of Epidemiology, Naval Medical University, 200433, Shanghai, China.
  • Wei GH; Institute of Bioinformatics, School of Basic Medical Science, Southern Medical University, 510515, Guangzhou, China.
  • Hou J; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, Human Phenome Institute, School of Life Sciences, Fudan University, 200438, Shanghai, China.
  • Jiang DK; Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, 90014, Oulu, Finland.
Nat Commun ; 13(1): 1232, 2022 03 09.
Article en En | MEDLINE | ID: mdl-35264579
Most cancer causal variants are found in gene regulatory elements, e.g., enhancers. However, enhancer variants predisposing to hepatocellular carcinoma (HCC) remain unreported. Here we conduct a genome-wide survey of HCC-susceptible enhancer variants through a three-stage association study in 11,958 individuals and identify rs73613962 (T > G) within the intronic region of PRMT7 at 16q22.1 as a susceptibility locus of HCC (OR = 1.41, P = 6.02 × 10-10). An enhancer dual-luciferase assay indicates that the rs73613962-harboring region has allele-specific enhancer activity. CRISPR-Cas9/dCas9 experiments further support the enhancer activity of this region to regulate PRMT7 expression. Mechanistically, transcription factor HNF4A binds to this enhancer region, with preference to the risk allele G, to promote PRMT7 expression. PRMT7 upregulation contributes to in vitro, in vivo, and clinical HCC-associated phenotypes, possibly by affecting the p53 signaling pathway. This concept of HCC pathogenesis may open a promising window for HCC prevention/treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína-Arginina N-Metiltransferasas / Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína-Arginina N-Metiltransferasas / Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido