LncRNA-AC006129.1 reactivates a SOCS3-mediated anti-inflammatory response through DNA methylation-mediated CIC downregulation in schizophrenia
| Autor: | Haiyan Ou, Xingbing Huang, Cunyou Zhao, Qiyang Li, Zelin Liu, Tingyun Jiang, Wei Jiang, Jian Zhang, Zhongju Wang, Zhuo Wang, Chaoying Ni, Yu Hou, Fengchun Wu, Xin-Hong Zhu, Sihan Liu, Wenquan Liang, Zhexing Wen, Xianzhen Zheng, Shuyun Li, Ence Yang, Qiong Yang, Bo Guo, Shufen Li |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Methyltransferase Down-Regulation Biology Mice 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation mental disorders Animals Humans Epigenetics Molecular Biology Inflammation RNA Promoter DNA Methylation Long non-coding RNA Psychiatry and Mental health 030104 developmental biology chemistry Suppressor of Cytokine Signaling 3 Protein DNA methylation Schizophrenia Cancer research RNA Long Noncoding 030217 neurology & neurosurgery DNA |
| Zdroj: | Molecular Psychiatry. 26:4511-4528 |
| ISSN: | 1476-5578 1359-4184 |
| DOI: | 10.1038/s41380-020-0662-3 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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