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Dysregulated m6A modification promotes lipogenesis and development of non-alcoholic fatty liver disease and hepatocellular carcinoma.
Yang, Yeming; Cai, Jingshu; Yang, Xue; Wang, Kaifang; Sun, Kuanxiang; Yang, Zhenglin; Zhang, Lin; Yang, Lu; Gu, Chun; Huang, Xiang; Wang, Ziyan; Zhu, Xianjun.
Afiliação
  • Yang Y; Health Management Center, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China; The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine, Center for Medical G
  • Cai J; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China.
  • Yang X; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China.
  • Wang K; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China.
  • Sun K; Health Management Center, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China; The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine, Center for Medical G
  • Yang Z; The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine, Center for Medical Genetics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China; School of Medicine, University of Ele
  • Zhang L; The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine, Center for Medical Genetics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China; School of Medicine, University of Ele
  • Yang L; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China.
  • Gu C; Department of Hepatobiliary & Pancreatic Center, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China; Department of Hepatobiliary & Pancreatic Center, Chinese Academy of Medical Sciences and Sichua
  • Huang X; Department of Urology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China. Electronic address: huangxiang@med.uestc.edu.cn.
  • Wang Z; Health Management Center, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China; The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine, Center for Medical G
  • Zhu X; Health Management Center, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China; The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine, Center for Medical G
Mol Ther ; 30(6): 2342-2353, 2022 06 01.
Article em En | MEDLINE | ID: mdl-35192934
ABSTRACT
Type 2 diabetes mellitus (DM2) is associated closely with non-alcoholic fatty liver disease (NAFLD) by affecting lipid metabolism, which may lead to non-alcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma (HCC). N6-methyladenosine (m6A) RNA methylation is an important epigenetic regulation for gene expression and is related to HCC development. We developed a new NAFLD model oriented from DM2 mouse, which spontaneously progressed to histological features of NASH, fibrosis, and HCC with high incidence. By RNA sequencing, protein expression and methylated RNA immunoprecipitation (MeRIP)-qPCR analysis, we found that enhanced expression of ACLY and SCD1 in this NAFLD model and human HCC samples was due to excessive m6A modification, but not elevation of mature SREBP1. Moreover, targeting METTL3/14 in vitro increases protein level of ACLY and SCD1 as well as triglyceride and cholesterol production and accumulation of lipid droplets. m6A sequencing analysis revealed that overexpressed METTL14 binds to mRNA of ACLY and SCD1 and alters their expression pattern. Our findings demonstrate a new NAFLD mouse model that provides a study platform for DM2-related NAFLD and reveals a unique epitranscriptional regulating mechanism for lipid metabolism via m6A-modified protein expression of ACLY and SCD1.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Diabetes Mellitus Tipo 2 / Hepatopatia Gordurosa não Alcoólica / Neoplasias Hepáticas Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Mol Ther Assunto da revista: BIOLOGIA MOLECULAR / TERAPEUTICA Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Diabetes Mellitus Tipo 2 / Hepatopatia Gordurosa não Alcoólica / Neoplasias Hepáticas Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Mol Ther Assunto da revista: BIOLOGIA MOLECULAR / TERAPEUTICA Ano de publicação: 2022 Tipo de documento: Article