Expression study of Wnt/β-catenin signaling pathway associated lncRNAs in schizophrenia

Abstract Schizophrenia is one of the most debilitating mental illnesses affecting any age group. The mechanism and etiology of schizophrenia are extremely complex and multiple signaling pathways recruit genes implicated in the etiology of this disease. While the role of Wnt/β-catenin signaling in th...

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Main Authors: Fatemeh Manafzadeh, Behzad Baradaran, Seyed Gholamreza Noor Azar, Kamran Javidi Aghdam, Reza Dabbaghipour, Asghar Shayannia, Soudeh Ghafouri-Fard
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Annals of General Psychiatry
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Online Access:https://doi.org/10.1186/s12991-025-00545-1
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author Fatemeh Manafzadeh
Behzad Baradaran
Seyed Gholamreza Noor Azar
Kamran Javidi Aghdam
Reza Dabbaghipour
Asghar Shayannia
Soudeh Ghafouri-Fard
author_facet Fatemeh Manafzadeh
Behzad Baradaran
Seyed Gholamreza Noor Azar
Kamran Javidi Aghdam
Reza Dabbaghipour
Asghar Shayannia
Soudeh Ghafouri-Fard
author_sort Fatemeh Manafzadeh
collection DOAJ
description Abstract Schizophrenia is one of the most debilitating mental illnesses affecting any age group. The mechanism and etiology of schizophrenia are extremely complex and multiple signaling pathways recruit genes implicated in the etiology of this disease. While the role of Wnt/β-catenin signaling in this disorder has been verified, the impact of long noncoding RNAs (lncRNAs) associated with this pathway has not been studied in schizophrenia. The objective of this study was to examine the expression levels of Wnt/β-catenin-related lncRNAs, namely CCAT2, SNHG5, PTCSC3, and DANCR, as well as the CTNNB1 gene encoding beta-catenin protein in two groups of schizophrenia patients (drug-naïve and medicated) compared with healthy individuals. This study included 50 medicated patients in the remission phase of the disease, 25 drug-naive patients in the acute phase, and 50 control subjects. There was no significant difference in CTNNB1 gene expression in the medicated patients compared to controls (P value = 0.9754). However, the expression of this gene was significantly decreased in drug-naïve first-episode patients compared with controls (P value < 0.001). In contrast, expression of DANCR, PTCSC3, SNHG5, and CCAT2 genes was significantly higher in medicated (P values < 0.001, < 0.001, = 0.01, < 0.001, respectively) and drug-naive first-episode patients (P value < 0.001) compared to control subjects. ROC curve analysis revealed that DANCR, PTCSC3, SNHG5, and CCAT2 genes had diagnostic power with specificity and sensitivity of 80% and above in separation between study subgroups. In brief, our data demonstrated dysregulation of Wnt/β pathway related genes and lncRNAs in the peripheral blood of patients with schizophrenia and their potential as biomarkers for this disorder.
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spelling doaj-art-b4a39858c2574a5895c44dfd5e82c92a2025-01-19T12:34:09ZengBMCAnnals of General Psychiatry1744-859X2025-01-0124111010.1186/s12991-025-00545-1Expression study of Wnt/β-catenin signaling pathway associated lncRNAs in schizophreniaFatemeh Manafzadeh0Behzad Baradaran1Seyed Gholamreza Noor Azar2Kamran Javidi Aghdam3Reza Dabbaghipour4Asghar Shayannia5Soudeh Ghafouri-Fard6Student Research Committee, School of Medicine, Shahroud University of Medical SciencesImmunology Research Center, Tabriz University of Medical SciencesResearch Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical SciencesStudent Research Committee, School of Medicine, Shahroud University of Medical SciencesDepartment of Medical Genetics, School of Medicine, Tehran University of Medical SciencesDepartment of Medical Biotechnology, School of Medicine, Shahroud University of Medical SciencesDepartment of Medical Genetics, Shahid Beheshti University of Medical SciencesAbstract Schizophrenia is one of the most debilitating mental illnesses affecting any age group. The mechanism and etiology of schizophrenia are extremely complex and multiple signaling pathways recruit genes implicated in the etiology of this disease. While the role of Wnt/β-catenin signaling in this disorder has been verified, the impact of long noncoding RNAs (lncRNAs) associated with this pathway has not been studied in schizophrenia. The objective of this study was to examine the expression levels of Wnt/β-catenin-related lncRNAs, namely CCAT2, SNHG5, PTCSC3, and DANCR, as well as the CTNNB1 gene encoding beta-catenin protein in two groups of schizophrenia patients (drug-naïve and medicated) compared with healthy individuals. This study included 50 medicated patients in the remission phase of the disease, 25 drug-naive patients in the acute phase, and 50 control subjects. There was no significant difference in CTNNB1 gene expression in the medicated patients compared to controls (P value = 0.9754). However, the expression of this gene was significantly decreased in drug-naïve first-episode patients compared with controls (P value < 0.001). In contrast, expression of DANCR, PTCSC3, SNHG5, and CCAT2 genes was significantly higher in medicated (P values < 0.001, < 0.001, = 0.01, < 0.001, respectively) and drug-naive first-episode patients (P value < 0.001) compared to control subjects. ROC curve analysis revealed that DANCR, PTCSC3, SNHG5, and CCAT2 genes had diagnostic power with specificity and sensitivity of 80% and above in separation between study subgroups. In brief, our data demonstrated dysregulation of Wnt/β pathway related genes and lncRNAs in the peripheral blood of patients with schizophrenia and their potential as biomarkers for this disorder.https://doi.org/10.1186/s12991-025-00545-1SchizophreniaAntipsychotic drugsWnt/β-catenin pathwayΒ-cateninlncRNA
spellingShingle Fatemeh Manafzadeh
Behzad Baradaran
Seyed Gholamreza Noor Azar
Kamran Javidi Aghdam
Reza Dabbaghipour
Asghar Shayannia
Soudeh Ghafouri-Fard
Expression study of Wnt/β-catenin signaling pathway associated lncRNAs in schizophrenia
Annals of General Psychiatry
Schizophrenia
Antipsychotic drugs
Wnt/β-catenin pathway
Β-catenin
lncRNA
title Expression study of Wnt/β-catenin signaling pathway associated lncRNAs in schizophrenia
title_full Expression study of Wnt/β-catenin signaling pathway associated lncRNAs in schizophrenia
title_fullStr Expression study of Wnt/β-catenin signaling pathway associated lncRNAs in schizophrenia
title_full_unstemmed Expression study of Wnt/β-catenin signaling pathway associated lncRNAs in schizophrenia
title_short Expression study of Wnt/β-catenin signaling pathway associated lncRNAs in schizophrenia
title_sort expression study of wnt β catenin signaling pathway associated lncrnas in schizophrenia
topic Schizophrenia
Antipsychotic drugs
Wnt/β-catenin pathway
Β-catenin
lncRNA
url https://doi.org/10.1186/s12991-025-00545-1
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