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LncRNA-AC006129.1 reactivates a SOCS3-mediated anti-inflammatory response through DNA methylation-mediated CIC downregulation in schizophrenia

by Xin-Hong, Zhu , Ou Haiyan , Zhang, Jian , Jiang, Wei , Wang, Zhongju , Jiang Tingyun , Huang Xingbing , Zhao Cunyou , Ni Chaoying , Liang Wenquan , Li, Shufen , Zheng Xianzhen , Li, Shuyun , Wen Zhexing , Guo, Bo , Hou, Yu , Yang, Qiong , Liu Sihan , Wang, Zhuo , Wu Fengchun , Li, Qiyang , Liu Zelin , Yang Ence

in Deoxyribonucleic acid / Derepression / DNA / DNA methylation / Epigenetics / Genetic disorders / Inflammation / Mental disorders / Peripheral blood / Ribonucleic acid / RNA / Schizophrenia / Transcription

2021

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LncRNA-AC006129.1 reactivates a SOCS3-mediated anti-inflammatory response through DNA methylation-mediated CIC downregulation in schizophrenia

2021

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LncRNA-AC006129.1 reactivates a SOCS3-mediated anti-inflammatory response through DNA methylation-mediated CIC downregulation in schizophrenia

2021

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Journal Article

LncRNA-AC006129.1 reactivates a SOCS3-mediated anti-inflammatory response through DNA methylation-mediated CIC downregulation in schizophrenia

Xin-Hong, Zhu,

Ou Haiyan,

Zhang, Jian,

Jiang, Wei,

Wang, Zhongju,

Jiang Tingyun,

Huang Xingbing,

Zhao Cunyou,

Ni Chaoying,

Liang Wenquan,

Li, Shufen,

Zheng Xianzhen,

Li, Shuyun,

Wen Zhexing,

Guo, Bo,

Hou, Yu,

Yang, Qiong,

Liu Sihan,

Wang, Zhuo,

Wu Fengchun,

Li, Qiyang,

Liu Zelin,

Yang Ence

2021

Overview

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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Publisher

Nature Publishing Group

Subject

Deoxyribonucleic acid

/ DNA