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

Molecular Psychiatry volume 26, pages 4511–4528 (2021)Cite this article

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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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Fig. 1: Association of AC006129.1 and its related genes with schizophrenia.
Fig. 2: AC006129.1-induced aberrant mouse behavior through the regulation of inflammatory response genes.
Fig. 3: AC006129.1 promoted DNA methylation-mediated CIC downregulation.
Fig. 4: Derepression of SOCS3 and CASP1 by AC006129.1-mediated CIC downregulation.
Fig. 5: Proposed model of the derepression of SOCS3 and CASP1 by AC006129.1-mediated CIC hypermethylation and downregulation.

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References

  1. Millan MJ, Andrieux A, Bartzokis G, Cadenhead K, Dazzan P, Fusar-Poli P, et al. Altering the course of schizophrenia: progress and perspectives. Nat Rev Drug Discov. 2016;15:485–515.

    CAS  PubMed  Google Scholar 

  2. Van OsJ, Kenis G, Rutten BP. The environment and schizophrenia. Nature. 2010;468:203–12.

    Google Scholar 

  3. Khandaker GM, Cousins L, Deakin J, Lennox BR, Yolken R, Jones PB. Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment. Lancet Psychiatry. 2015;2:258–70.

    PubMed  PubMed Central  Google Scholar 

  4. Feigenson KA, Kusnecov AW, Silverstein SM. Inflammation and the two-hit hypothesis of schizophrenia. Neurosci Biobehav Rev. 2014;38:72–93.

    PubMed  Google Scholar 

  5. Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012;81:145–66.

    CAS  PubMed  Google Scholar 

  6. Lin H, Jiang M, Liu L, Yang Z, Ma Z, Liu S, et al. The long noncoding RNA Lnczc3h7a promotes a TRIM25-mediated RIG-I antiviral innate immune response. Nat Immunol. 2019;20:812–23.

    CAS  PubMed  Google Scholar 

  7. Briggs JA, Wolvetang EJ, Mattick JS, Rinn JL, Barry G. Mechanisms of long non-coding RNAs in mammalian nervous system development, plasticity, disease, and evolution. Neuron. 2015;88:861–77.

    CAS  PubMed  Google Scholar 

  8. Mathy NW, Chen XM. Long non-coding RNAs (lncRNAs) and their transcriptional control of inflammatory responses. J Biol Chem. 2017;292:12375–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Na KS, Jung HY, Kim YK. The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia. Prog neuro-Psychopharmacol Biol psychiatry. 2014;48:277–86.

    CAS  Google Scholar 

  10. The Network Pathway Analysis Subgroup of the Psychiatric Genomics C. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways. Nat Neurosci. 2015;18:199–209.

    Google Scholar 

  11. Richard MD, Brahm NC. Schizophrenia and the immune system: pathophysiology, prevention, and treatment. Am J Health Syst Pharm. 2012;69:757–66.

    CAS  PubMed  Google Scholar 

  12. Drexhage RC, Hoogenboezem TA, Cohen D, Versnel MA, Nolen WA, van Beveren NJ, et al. An activated set point of T-cell and monocyte inflammatory networks in recent-onset schizophrenia patients involves both pro- and anti-inflammatory forces. Int J Neuropsychopharmacol. 2011;14:746–55.

    CAS  PubMed  Google Scholar 

  13. Jones KA, Thomsen C. The role of the innate immune system in psychiatric disorders. Mol Cell Neurosci. 2013;53:52–62.

    CAS  PubMed  Google Scholar 

  14. Lawrence T, Natoli G. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol. 2011;11:750–61.

    CAS  PubMed  Google Scholar 

  15. Cianciulli A, Calvello R, Porro C, Trotta T, Panaro MA. Understanding the role of SOCS signaling in neurodegenerative diseases: current and emerging concepts. Cytokine Growth Factor Rev. 2017;37:67–79.

    CAS  PubMed  Google Scholar 

  16. Qin H, Wilson CA, Roberts KL, Baker BJ, Zhao X, Benveniste EN. IL-10 inhibits lipopolysaccharide-induced CD40 gene expression through induction of suppressor of cytokine signaling-3. J Immunol. 2006;177:7761–71.

    CAS  PubMed  Google Scholar 

  17. Baker BJ, Akhtar LN, Benveniste EN. SOCS1 and SOCS3 in the control of CNS immunity. Trends Immunol. 2009;30:392–400.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Chew CL, Conos SA, Unal B, Tergaonkar V. Noncoding RNAs: master regulators of inflammatory signaling. Trends Mol Med. 2018;24:66–84.

    CAS  PubMed  Google Scholar 

  19. Du M, Yuan L, Tan X, Huang D, Wang X, Zheng Z, et al. The LPS-inducible lncRNA Mirt2 is a negative regulator of inflammation. Nat Commun. 2017;8:2049.

    PubMed  PubMed Central  Google Scholar 

  20. Li H, Li Q, Guo T, He W, Dong C, Wang Y. LncRNA CRNDE triggers inflammation through the TLR3-NF-kappaB-cytokine signaling pathway. Tumour Biol. 2017;39:1010428317703821.

    PubMed  Google Scholar 

  21. Liu S, Wang Z, Chen D, Zhang B, Tian RR, Wu J, et al. Annotation and cluster analysis of spatiotemporal- and sex-related lncRNA expression in rhesus macaque brain. Genome Res. 2017;27:1608–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Schmitz KM, Mayer C, Postepska A, Grummt I. Interaction of noncoding RNA with the rDNA promoter mediates recruitment of DNMT3b and silencing of rRNA genes. Genes Dev. 2010;24:2264–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Deng Y, Luan S, Zhang Q, Xiao Y. Long noncoding RNA THRIL contributes in lipopolysaccharide-induced HK-2 cells injury by sponging miR-34a. J Cell Biochem. 2018;120:1–13.

  24. Barry G, Briggs JA, Vanichkina DP, Poth EM, Beveridge NJ, Ratnu VS, et al. The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing. Mol Psychiatry. 2014;19:486–94.

    CAS  PubMed  Google Scholar 

  25. Zhuo C, Hou W, Hu L, Lin C, Chen C, Lin X. Genomic editing of non-coding RNA genes with CRISPR/Cas9 ushers in a potential novel approach to study and treat schizophrenia. Front Mol Neurosci. 2017;10:28.

    PubMed  PubMed Central  Google Scholar 

  26. Tian T, Wei Z, Chang X, Liu Y, Gur RE, Sleiman PMA, et al. The long noncoding RNA landscape in amygdala tissues from schizophrenia patients. EBioMedicine. 2018;34:171–81.

    PubMed  PubMed Central  Google Scholar 

  27. Katsel P, Roussos P, Fam P, Khan S, Tan W, Hirose T, et al. The expression of long noncoding RNA NEAT1 is reduced in schizophrenia and modulates oligodendrocytes transcription. NPJ Schizophr. 2019;5:3.

    PubMed  PubMed Central  Google Scholar 

  28. Gandal MJ, Zhang P, Hadjimichael E, Walker RL, Chen C, Liu S, et al. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science. 2018;362:eaat8127.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Robinson MD, McCarthy DJ, Smyth GK. edgeR: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26:139–40.

    CAS  PubMed  Google Scholar 

  30. Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinforma. 2008;9:559.

    Google Scholar 

  31. Lin J, Wen Y, He S, Yang X, Zhang H, Zhu H. Pipelines for cross-species and genome-wide prediction of long noncoding RNA binding. Nat Protoc. 2019;14:795–818.

    CAS  PubMed  Google Scholar 

  32. Wang J, Duncan D, Shi Z, Zhang B. WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013. Nucleic Acids Res. 2013;41:W77–83.

    PubMed  PubMed Central  Google Scholar 

  33. Fromer M, Roussos P, Sieberts SK, Johnson JS, Kavanagh DH, Perumal TM, et al. Gene expression elucidates functional impact of polygenic risk for schizophrenia. Nat Neurosci. 2016;19:1442–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Liu Y, Chang X, Hahn CG, Gur RE, Sleiman PAM, Hakonarson H. Non-coding RNA dysregulation in the amygdala region of schizophrenia patients contributes to the pathogenesis of the disease. Transl Psychiatry. 2018;8:44.

    PubMed  PubMed Central  Google Scholar 

  35. Fillman SG, Cloonan N, Catts VS, Miller LC, Wong J, McCrossin T, et al. Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia. Mol Psychiatry. 2013;18:206–14.

    CAS  PubMed  Google Scholar 

  36. Wu Y, Yao YG, Luo XJ. SZDB: a database for schizophrenia genetic research. Schizophr Bull. 2017;43:459–71.

    PubMed  Google Scholar 

  37. Duan J, Goring HHH, Sanders AR, Moy W, Freda J, Drigalenko EI, et al. Transcriptomic signatures of schizophrenia revealed by dopamine perturbation in an ex vivo model. Transl Psychiatry. 2018;8:158.

    PubMed  PubMed Central  Google Scholar 

  38. Sanders AR, Drigalenko EI, Duan J, Moy W, Freda J, Goring HHH, et al. Transcriptome sequencing study implicates immune-related genes differentially expressed in schizophrenia: new data and a meta-analysis. Transl Psychiatry. 2017;7:e1093.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. GTEx Consortium, Laboratory, Data Analysis & Coordinating Center (LDACC)—Analysis Working Group, Statistical Methods groups—Analysis Working Group, Enhancing GTEx (eGTEx) groups, NIH Common Fund, et al. Genetic effects on gene expression across human tissues. Nature. 2017;550:204–13.

    Google Scholar 

  40. Wang H, Liu F, Chen W, Sun X, Cui W, Dong Z, et al. Genetic recovery of ErbB4 in adulthood partially restores brain functions in null mice. Proc Natl Acad Sci USA. 2018;115:13105–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Tang H, Hammack C, Ogden SC, Wen Z, Qian X, Li Y, et al. Zika virus infects human cortical neural progenitors and attenuates their growth. Cell Stem Cell. 2016;18:587–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Wen Z, Nguyen HN, Guo Z, Lalli MA, Wang X, Su Y, et al. Synaptic dysregulation in a human iPS cell model of mental disorders. Nature. 2014;515:414–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Xu M, Lee EM, Wen Z, Cheng Y, Huang WK, Qian X, et al. Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nat Med. 2016;22:1101–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Wang X, Ye F, Wen Z, Guo Z, Yu C, Huang WK et al. Structural interaction between DISC1 and ATF4 underlying transcriptional and synaptic dysregulation in an iPSC model of mental disorders. Mol Psychiatry. 2019. https://doi.org/10.1038/s41380-019-0485-2.

  45. Bentea E, Depasquale EAK, O’Donovan SM, Sullivan CR, Simmons M, Meador-Woodruff JH, et al. Kinase network dysregulation in a human induced pluripotent stem cell model of DISC1 schizophrenia. Mol omics. 2019;15:173–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. McQuade A, Coburn M, Tu CH, Hasselmann J, Davtyan H, Blurton-Jones M. Development and validation of a simplified method to generate human microglia from pluripotent stem cells. Mol Neurodegener. 2018;13:67.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Kim E, Lu HC, Zoghbi HY, Song JJ. Structural basis of protein complex formation and reconfiguration by polyglutamine disease protein Ataxin-1 and Capicua. Genes Dev. 2013;27:590–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Orefice LL, Zimmerman AL, Chirila AM, Sleboda SJ, Head JP, Ginty DD. Peripheral mechanosensory neuron dysfunction underlies tactile and behavioral deficits in mouse models of ASDs. Cell. 2016;166:299–313.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhao C, Xu Z, Chen J, Yu Z, Tong KL, Lo WS, et al. Two isoforms of GABA(A) receptor beta2 subunit with different electrophysiological properties: Differential expression and genotypical correlations in schizophrenia. Mol Psychiatry. 2006;11:1092–105.

    CAS  PubMed  Google Scholar 

  50. Alkelai A, Lupoli S, Greenbaum L, Kohn Y, Kanyas-Sarner K, Ben-Asher E, et al. DOCK4 and CEACAM21 as novel schizophrenia candidate genes in the Jewish population. Int J Neuropsychopharmacol. 2012;15:459–69.

    CAS  PubMed  Google Scholar 

  51. Fang S, Zhang L, Guo J, Niu Y, Wu Y, Li H, et al. NONCODEV5: a comprehensive annotation database for long non-coding RNAs. Nucleic Acids Res. 2018;46:D308–D314.

    CAS  PubMed  Google Scholar 

  52. Mas-Ponte D, Carlevaro-Fita J, Palumbo E, Hermoso Pulido T, Guigo R, Johnson R. LncATLAS database for subcellular localization of long noncoding RNAs. RNA. 2017;23:1080–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Wong ML, Inserra A, Lewis MD, Mastronardi CA, Leong L, Choo J, et al. Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition. Mol Psychiatry. 2016;21:797–805.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Calcia MA, Bonsall DR, Bloomfield PS, Selvaraj S, Barichello T, Howes OD. Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness. Psychopharmacology. 2016;233:1637–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Lee CJ, Chan WI, Cheung M, Cheng YC, Appleby VJ, Orme AT, et al. CIC, a member of a novel subfamily of the HMG-box superfamily, is transiently expressed in developing granule neurons. Brain Res Mol Brain Res. 2002;106:151–6.

    CAS  PubMed  Google Scholar 

  56. Franzen O, Gan LM, Bjorkegren JLM. PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data. Database. 2019;2019:baz046.

    PubMed  PubMed Central  Google Scholar 

  57. Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR, O’Keeffe S, et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci. 2014;34:11929–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Fores M, Simon-Carrasco L, Ajuria L, Samper N, Gonzalez-Crespo S, Drosten M, et al. A new mode of DNA binding distinguishes Capicua from other HMG-box factors and explains its mutation patterns in cancer. PLoS Genet. 2017;13:e1006622.

    PubMed  PubMed Central  Google Scholar 

  59. Nakagawa Y, Chiba K. Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia. J Pharm Exp Ther. 2016;358:504–15.

    CAS  Google Scholar 

  60. Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511:421–7.

    PubMed Central  Google Scholar 

  61. Yuan N, Chen Y, Xia Y, Dai J, Liu C. Inflammation-related biomarkers in major psychiatric disorders: a cross-disorder assessment of reproducibility and specificity in 43 meta-analyses. Transl Psychiatry. 2019;9:233.

    PubMed  PubMed Central  Google Scholar 

  62. Lu HC, Tan Q, Rousseaux MW, Wang W, Kim JY, Richman R, et al. Disruption of the ATXN1-CIC complex causes a spectrum of neurobehavioral phenotypes in mice and humans. Nat Genet. 2017;49:527–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Kim E, Park S, Choi N, Lee J, Yoe J, Kim S, et al. Deficiency of Capicua disrupts bile acid homeostasis. Sci Rep. 2015;5:8272.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Qin H, Yeh WI, De Sarno P, Holdbrooks AT, Liu Y, Muldowney MT, et al. Signal transducer and activator of transcription-3/suppressor of cytokine signaling-3 (STAT3/SOCS3) axis in myeloid cells regulates neuroinflammation. Proc Natl Acad Sci USA. 2012;109:5004–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Kirkpatrick B, Miller BJ. Inflammation and schizophrenia. Schizophr Bull. 2013;39:1174–9.

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We are grateful to Dr Huda Y. Zoghbi, and Ji-Joon Song for the gift of the pUAST-CIC plasmid. We thank the National Natural Science Foundation of China [grant number 81871049, 81671333], the Guangdong Science and Technology Foundation [grant number 2019B030316032], and Guangzhou Science Technology and Innovation Commission [grant number 201804010259, 201807010064] for providing financial supports. We thank the individuals for their willingness to participate in this study. We thank Center for Applied Genomics, the Children’s Hospital of Philadelphia for sharing postmortem brain RNA-seq dataset (https://www.ncbi.nlm.nih.gov/sra/?term=SRP102186). We also thank the NIMH Repository and Genomics Resources approve our request for data generated by the CMC. The requested data were generated as part of the CMC supported by funding from Takeda Pharmaceuticals Company Limited, F. Hoffman-La Roche Ltd., and NIH grants R01MH085542, R01MH093725, P50MH066392, P50MH080405, R01MH097276, RO1-MH-075916, P50M096891, P50MH084053S1, R37MH057881 and R37MH057881S1, HHSN271201300031C, AG02219, AG05138, and MH06692. Brain tissue for the study was obtained from the following brain bank collections: the Mount Sinai NIH Brain and Tissue Repository, the University of Pennsylvania Alzheimer’s Disease Core Center, the University of Pittsburgh NeuroBioBank and Brain and Tissue Repositories, and the NIMH Human Brain Collection Core. CMC Leadership: Pamela Sklar, Joseph Buxbaum (Icahn School of Medicine at Mount Sinai), Bernie Devlin, David Lewis (University of Pittsburgh), Raquel Gur, Chang-Gyu Hahn (University of Pennsylvania), Keisuke Hirai, Hiroyoshi Toyoshiba (Takeda Pharmaceuticals Company Limited), Enrico Domenici, Laurent Essioux (F. Hoffman-La Roche Ltd), Lara Mangravite, Mette Peters (Sage Bionetworks), Thomas Lehner, Barbara Lipska (NIMH).

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  1. These authors contributed equally: Chaoying Ni, Wei Jiang, Zhongju Wang

Authors and Affiliations

  1. 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

    Chaoying Ni, Wei Jiang, Zhongju Wang, Jian Zhang, Haiyan Ou, Wenquan Liang, Qiyang Li, Yu Hou, Bo Guo, Shufen Li & Cunyou Zhao

  2. 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

    Chaoying Ni, Wei Jiang, Zhongju Wang, Zhuo Wang, Haiyan Ou, Qiyang Li, Bo Guo, Shufen Li, Xin-Hong Zhu & Cunyou Zhao

  3. Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

    Zhuo Wang & Xin-Hong Zhu

  4. Guangdong General Hospital, Guangdong Academy of Medical Science and Guangdong Mental Health Center, Guangzhou, China

    Xianzhen Zheng

  5. Institute of Systems Biomedicine, Department of Medical Bioinformatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China

    Zelin Liu & Ence Yang

  6. The Third People’s Hospital of Zhongshan, Zhongshan, Guangdong, China

    Tingyun Jiang

  7. Department of Psychiatry, the Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, Guangdong, China

    Fengchun Wu, Qiong Yang, Shuyun Li & Xingbing Huang

  8. Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China

    Sihan Liu

  9. Departments of Psychiatry and Behavior Sciences, Cell Biology, and Neurology, Emory University, Atlanta, GA, USA

    Zhexing Wen

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  1. Chaoying Ni
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Contributions

Conceived and designed the experiments: CN, WJ and CZ. Performed the experiments: CN, WJ, ZW, WL, QL, YH, BG and SL. Analyzed the data: CN, WJ, ZW, JZ, ZL, HO, SL, EY, XZ, ZW and CZ. Collected and diagnosed the control and patient subjects: XZ, TJ, FW, QY, SL and XH. Wrote the paper: CN, WJ, ZW and CZ.

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Correspondence to Cunyou Zhao.

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Ni, C., Jiang, W., Wang, Z. et al. LncRNA-AC006129.1 reactivates a SOCS3-mediated anti-inflammatory response through DNA methylation-mediated CIC downregulation in schizophrenia. Mol Psychiatry 26, 4511–4528 (2021). https://doi.org/10.1038/s41380-020-0662-3

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