title: The early growth response protein 1-miR-30a-5p-neurogenic differentiation factor 1 axis as a novel biomarker for schizophrenia diagnosis and treatment monitoring.
abstract: To date, diagnosis of schizophrenia is still based on clinical interviews and careful observations, which is subjective and variable, and can lead to misdiagnosis and/or delay in diagnosis. As early intervention in schizophrenia is important in improving outcomes, objective tests that can be used for schizophrenia diagnosis or treatment monitoring are thus in great need. MicroRNAs (miRNAs) negatively regulate target gene expression and their biogenesis is tightly controlled by various factors including transcription factors (TFs). Dysregulation of miRNAs in brain tissue and peripheral blood mononuclear cells (PBMNCs) from patients with schizophrenia has been well documented, but analysis of the sensitivity and specificity for potential diagnostic utility of these alternations is limited. In this study, we explored the TF-miRNA-30-target gene axis as a novel biomarker for schizophrenia diagnosis and treatment monitoring. Using bioinformatics analysis, we retrieved all TFs that control the biogenesis of miRNA 30 members as well as all target genes that are regulated by miRNA-30 members. Further, reverse transcription-quantitative PCR analysis revealed that the early growth response protein 1 (EGR1) and miR-30a-5p were remarkably downregulated, whereas neurogenic differentiation factor 1 (NEUROD1) was significantly upregulated in PBMNCs from patients in acute psychotic state. Antipsychotics treatment resulted in the elevation of EGR1 and miR-30a-5p but the reduction of NEUROD1. Receiver operating characteristic analysis showed that the EGR1-miR-30a-5p-NEUROD1 axis possessed significantly greater diagnostic value than miR-30a-5p alone. Our data suggest the EGR1-miR-30a-5p-NEUROD1 axis might serve as a promising biomarker for diagnosis and treatment monitoring for those patients in acute psychotic state.
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.affiliation: Wuxi Mental Health Center, Wuxi, China.
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Unit on Statistical Genomics, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Shugart
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, China.
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: N
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: C
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.|First Clinical Medical College of Shanxi Medical University, Taiyuan, China.
authors.forename: X
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.|First Clinical Medical College of Shanxi Medical University, Taiyuan, China.
authors.forename: J
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.|First Clinical Medical College of Shanxi Medical University, Taiyuan, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.|First Clinical Medical College of Shanxi Medical University, Taiyuan, China.
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.|First Clinical Medical College of Shanxi Medical University, Taiyuan, China.
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, China.
authors.forename: T
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.|First Clinical Medical College of Shanxi Medical University, Taiyuan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015415:Biomarkers; D016022:Case-Control Studies; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D012559:Schizophrenia / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D051766:Early Growth Response Protein 1; D035683:MicroRNAs; C497325:EGR1 protein, human; C546086:MIRN30b microRNA, human; C093970:NEUROD1 protein, human