ArticleMolecular psychiatry2021
LncRNA-AC006129.1 reactivates a SOCS3-mediated anti-inflammatory response through DNA methylation-mediated CIC downregulation in schizophrenia.
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Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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35 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- A Review on the Expression Pattern of Non-coding RNAs in Patients With Schizophrenia: With a Special Focus on Peripheral Blood as a Source of Expression Analysis.Frontiers in psychiatry · 2021Pooled it
- Genetic and functional insights into long noncoding RNAs in schizophrenia.Molecular psychiatry · 2026Article
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- Peripheral lncRNA-IL1RAP Dysregulation in Schizophrenia: A Multi-Omics Bridge Between Immunity and Diagnosis.Brain and behavior · 2026Article
- Integrative ceRNA network analysis in monozygotic twins reveals shared and disorder-specific molecular signatures in major psychiatric disorders.BMC psychiatry · 2026Article
- Janus kinase/signal transducer and activator of transcription pathway in schizophrenia (Review).Biomedical reports · 2026Review
- Allele-Specific Methylation Links Non-coding Variant of rs2280906 to MYOM2 Regulation in Schizophrenia.Molecular neurobiology · 2025Article
- A non-coding RNA risk pathway in schizophrenia: miR-137 enhances the lncRNA GOMAFU through a pathological transcription network.Translational psychiatry · 2025Article
- Gain of Alternative Allele Expression of LINC02449 at rs149707223 in Schizophrenia and Bipolar Disorder: Inducing Synaptic Transmission and Behavioral Deficits in Mice.Nature communications · 2025Article
- Molecular and Clinical Considerations for Anesthesia in the Aging Brain.International journal of molecular sciences · 2025Review
- LncRNA-miRNA‒mRNA Network in Schizophrenia.Journal of molecular neuroscience : MN · 2025Article
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- Long Non-Coding RNAs: Key Regulators of Tumor Epithelial/Mesenchymal Plasticity and Cancer Stemness.Cells · 2025Review
- HERV-W Env Induces Neuron Pyroptosis via the NLRP3-CASP1-GSDMD Pathway in Recent-Onset Schizophrenia.International journal of molecular sciences · 2025Article
- Deciphering transcriptomic signatures in schizophrenia, bipolar disorder, and major depressive disorder.Frontiers in psychiatry · 2025Article
- Gain of bipolar disorder-related lncRNA AP1AR-DT in mice induces depressive and anxiety-like behaviors by reducing Negr1-mediated excitatory synaptic transmission.BMC medicine · 2024Article
- Article
- Transition of allele-specific DNA hydroxymethylation at regulatory loci is associated with phenotypic variation in monozygotic twins discordant for psychiatric disorders.BMC medicine · 2023Article
- The human lncRNA GOMAFU suppresses neuronal interferon response pathways affected in neuropsychiatric diseases.Brain, behavior, and immunity · 2023Article
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Authors and funding
23 authors at 8 institutions in 3 countries.
Chaoying Ni *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.
Wei Jiang *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.
Zhongju Wang *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.
Zhuo WangKey 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.
Jian ZhangDepartment 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.
Xianzhen ZhengGuangdong General Hospital, Guangdong Academy of Medical Science and Guangdong Mental Health Center, Guangzhou, China.
Zelin LiuInstitute of Systems Biomedicine, Department of Medical Bioinformatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Haiyan OuDepartment 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.
Tingyun JiangThe Third People's Hospital of Zhongshan, Zhongshan, Guangdong, China.
Wenquan LiangDepartment 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.
Fengchun WuDepartment of Psychiatry, the Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, Guangdong, China.
Qiyang LiDepartment 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.
Yu HouDepartment 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.
Qiong YangDepartment of Psychiatry, the Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, Guangdong, China.
Bo GuoDepartment 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.
Sihan LiuCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
Shuyun LiDepartment of Psychiatry, the Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, Guangdong, China.
Shufen LiDepartment 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.
Ence YangInstitute of Systems Biomedicine, Department of Medical Bioinformatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.ORCID http://orcid.org/0000-0002-9526-2737
Xin-Hong ZhuKey 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.ORCID http://orcid.org/0000-0002-9059-5321
Xingbing HuangDepartment of Psychiatry, the Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, Guangdong, China.
Zhexing WenDepartments of Psychiatry and Behavior Sciences, Cell Biology, and Neurology, Emory University, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-1518-3845
Cunyou ZhaoDepartment 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. cyzhao@smu.edu.cn.ORCID http://orcid.org/0000-0001-6116-4584
Southern Medical University · CNGuangzhou Medical University · CNPeking University · CNCentral South University · CNEmory University · USGuangdong General Hospital · CNMinistry of Education · RWZhongshan People's Hospital · CN
Funding
White Matter Abnormalities in SchizophreniaP50MH066392 · NIMH · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI O'DONOVAN, MICHAEL J · 2002 to 2012
$18.6MProject 5: In vivo measurement of GABA transmission in healthy controls & subjectP50MH084053 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEWIS, DAVID A · 2008 to 2012
$11.5MInternational Cohort Collection for Bipolar DisorderR01MH085542 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI SMOLLER, JORDAN W · 2008 to 2012
$10.7MNMDA Receptor Hypofunction in the Amygdala of Schizophrenia PatientsP50MH096891 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI BILKER, WARREN B. · 2012 to 2016
$10.6MGenetics Association in Schizophrenia and Other DisordersR37MH057881 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DEVLIN, BERNIE · 2013 to 2022
$5.4MSrc mediates molecular alterations leading to NMDAR hypofunction in schizophreniaR01MH075916 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI BORGMANN-WINTER, KARIN, HAHN, CHANG-GYU · 2006 to 2019
$3.3MIdentifying therapeutic targets for autism using Shank3-deficient miceR01MH093725 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BUXBAUM, JOSEPH D. · 2011 to 2015
$2.5M1/3-Networks from Multidimensional Data for Schizophrenia and Related DisordersR01MH097276 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SCHADT, ERIC E, SKLAR, PAMELA · 2012 to 2014
$2.5MNIDA NIH HHS HHSN271201300031CNIMH NIH HHS P50 MH066392NIMH NIH HHS P50 MH084053NIMH NIH HHS P50 MH096891NIMH NIH HHS R01 MH075916NIMH NIH HHS R01 MH085542NIMH NIH HHS R01 MH093725NIMH NIH HHS R01 MH097276NIMH NIH HHS R37 MH057881
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.
Indexed as
DNA MethylationRNA, Long NoncodingSchizophreniaSuppressor of Cytokine Signaling 3 ProteinAnimalsDown-RegulationHumansInflammationMiceRNA, Long NoncodingSOCS3 protein, humanSocs3 protein, mouseSuppressor of Cytokine Signaling 3 Protein
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