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LncRNA-AC006129.1 reactivates a SOCS3-mediated anti-inflammatory response through DNA methylation-mediated CIC downregulation in schizophrenia.
Ni, Chaoying; Jiang, Wei; Wang, Zhongju; Wang, Zhuo; Zhang, Jian; Zheng, Xianzhen; Liu, Zelin; Ou, Haiyan; Jiang, Tingyun; Liang, Wenquan; Wu, Fengchun; Li, Qiyang; Hou, Yu; Yang, Qiong; Guo, Bo; Liu, Sihan; Li, Shuyun; Li, Shufen; Yang, Ence; Zhu, Xin-Hong; Huang, Xingbing; Wen, Zhexing; Zhao, Cunyou.
Afiliação
  • Ni C; Department of Medical Genetics, School of Basic Medical Sciences, Guangdong Technology and Engineering Research Center for Molecular Diagnostics of Human Genetic Diseases, and Guangdong Engineering and Technology Research Center for Genetic Testing, Southern Medical University, Guangzhou, China.
  • Jiang W; Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, and Guangdong Province Key Laboratory of Psychiatric Disorders, Southern Medical University, Guangzhou, Guangdong, China.
  • Wang Z; Department of Medical Genetics, School of Basic Medical Sciences, Guangdong Technology and Engineering Research Center for Molecular Diagnostics of Human Genetic Diseases, and Guangdong Engineering and Technology Research Center for Genetic Testing, Southern Medical University, Guangzhou, China.
  • Wang Z; Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, and Guangdong Province Key Laboratory of Psychiatric Disorders, Southern Medical University, Guangzhou, Guangdong, China.
  • Zhang J; Department of Medical Genetics, School of Basic Medical Sciences, Guangdong Technology and Engineering Research Center for Molecular Diagnostics of Human Genetic Diseases, and Guangdong Engineering and Technology Research Center for Genetic Testing, Southern Medical University, Guangzhou, China.
  • Zheng X; Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, and Guangdong Province Key Laboratory of Psychiatric Disorders, Southern Medical University, Guangzhou, Guangdong, China.
  • Liu Z; Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, and Guangdong Province Key Laboratory of Psychiatric Disorders, Southern Medical University, Guangzhou, Guangdong, China.
  • Ou H; Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • Jiang T; Department of Medical Genetics, School of Basic Medical Sciences, Guangdong Technology and Engineering Research Center for Molecular Diagnostics of Human Genetic Diseases, and Guangdong Engineering and Technology Research Center for Genetic Testing, Southern Medical University, Guangzhou, China.
  • Liang W; Guangdong General Hospital, Guangdong Academy of Medical Science and Guangdong Mental Health Center, Guangzhou, China.
  • Wu F; Institute of Systems Biomedicine, Department of Medical Bioinformatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
  • Li Q; Department of Medical Genetics, School of Basic Medical Sciences, Guangdong Technology and Engineering Research Center for Molecular Diagnostics of Human Genetic Diseases, and Guangdong Engineering and Technology Research Center for Genetic Testing, Southern Medical University, Guangzhou, China.
  • Hou Y; Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, and Guangdong Province Key Laboratory of Psychiatric Disorders, Southern Medical University, Guangzhou, Guangdong, China.
  • Yang Q; The Third People's Hospital of Zhongshan, Zhongshan, Guangdong, China.
  • Guo B; Department of Medical Genetics, School of Basic Medical Sciences, Guangdong Technology and Engineering Research Center for Molecular Diagnostics of Human Genetic Diseases, and Guangdong Engineering and Technology Research Center for Genetic Testing, Southern Medical University, Guangzhou, China.
  • Liu S; Department of Psychiatry, the Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, Guangdong, China.
  • Li S; Department of Medical Genetics, School of Basic Medical Sciences, Guangdong Technology and Engineering Research Center for Molecular Diagnostics of Human Genetic Diseases, and Guangdong Engineering and Technology Research Center for Genetic Testing, Southern Medical University, Guangzhou, China.
  • Li S; Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, and Guangdong Province Key Laboratory of Psychiatric Disorders, Southern Medical University, Guangzhou, Guangdong, China.
  • Yang E; Department of Medical Genetics, School of Basic Medical Sciences, Guangdong Technology and Engineering Research Center for Molecular Diagnostics of Human Genetic Diseases, and Guangdong Engineering and Technology Research Center for Genetic Testing, Southern Medical University, Guangzhou, China.
  • Zhu XH; Department of Psychiatry, the Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, Guangdong, China.
  • Huang X; Department of Medical Genetics, School of Basic Medical Sciences, Guangdong Technology and Engineering Research Center for Molecular Diagnostics of Human Genetic Diseases, and Guangdong Engineering and Technology Research Center for Genetic Testing, Southern Medical University, Guangzhou, China.
  • Wen Z; Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, and Guangdong Province Key Laboratory of Psychiatric Disorders, Southern Medical University, Guangzhou, Guangdong, China.
  • Zhao C; Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
Mol Psychiatry ; 26(8): 4511-4528, 2021 08.
Article em En | MEDLINE | ID: mdl-32015466
ABSTRACT
Schizophrenia is a complex genetic disorder, the non-Mendelian features of which are likely complicated by epigenetic factors yet to be elucidated. Here, we performed RNA sequencing of peripheral blood RNA from monozygotic twins discordant for schizophrenia, and identified a schizophrenia-associated upregulated long noncoding RNA (lncRNA, AC006129.1) that participates in the inflammatory response by enhancing SOCS3 and CASP1 expression in schizophrenia patients and further validated this finding in AC006129.1-overexpressing mice showing schizophrenia-related abnormal behaviors. We find that AC006129.1 binds to the promoter region of the transcriptional repressor Capicua (CIC), facilitates the interactions of DNA methyltransferases with the CIC promoter, and promotes DNA methylation-mediated CIC downregulation, thereby ameliorating CIC-induced SOCS3 and CASP1 repression. Derepression of SOCS3 enhances the anti-inflammatory response by inhibiting JAK/STAT-signaling activation. Our findings reveal an epigenetic mechanism with etiological and therapeutic implications for schizophrenia.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Esquizofrenia / Metilação de DNA / RNA Longo não Codificante / Proteína 3 Supressora da Sinalização de Citocinas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Mol Psychiatry Assunto da revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China
Texto completo
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XML
PubMed Links
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Esquizofrenia / Metilação de DNA / RNA Longo não Codificante / Proteína 3 Supressora da Sinalização de Citocinas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Mol Psychiatry Assunto da revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China