title: Exploring Transcription Factors-microRNAs Co-regulation Networks in Schizophrenia.
abstract: Transcriptional factors (TFs) and microRNAs (miRNAs) have been recognized as 2 classes of principal gene regulators that may be responsible for genome coexpression changes observed in schizophrenia (SZ).
  
  
  
  This study aims to (1) identify differentially coexpressed genes (DCGs) in 3 mRNA expression microarray datasets; (2) explore potential interactions among the DCGs, and differentially expressed miRNAs identified in our dataset composed of early-onset SZ patients and healthy controls; (3) validate expression levels of some key transcripts; and (4) explore the druggability of DCGs using the curated database.
  
  
  
  We detected a differential coexpression network associated with SZ and found that 9 out of the 12 regulators were replicated in either of the 2 other datasets. Leveraging the differentially expressed miRNAs identified in our previous dataset, we constructed a miRNA-TF-gene network relevant to SZ, including an EGR1-miR-124-3p-SKIL feed-forward loop. Our real-time quantitative PCR analysis indicated the overexpression of miR-124-3p, the under expression of SKIL and EGR1 in the blood of SZ patients compared with controls, and the direction of change of miR-124-3p and SKIL mRNA levels in SZ cases were reversed after a 12-week treatment cycle. Our druggability analysis revealed that many of these genes have the potential to be drug targets.
  
  
  
  Together, our results suggest that coexpression network abnormalities driven by combinatorial and interactive action from TFs and miRNAs may contribute to the development of SZ and be relevant to the clinical treatment of the disease.
authors.affiliation: Department of Psychiatry, First Clinical Medical College/First Hospital of Shanxi Medical University, Taiyuan, China;
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Psychiatry, Institute of Mental Health, Sixth Hospital, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, China;
authors.forename: Weihua
authors.initials: W
authors.lastname: Yue
authors.affiliation: Unit on Statistical Genomics, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD;
authors.forename: Yin
authors.initials: Y
authors.lastname: Yao Shugart
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China;
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China;
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.affiliation: Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai, China;
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Psychiatry, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, China.
authors.forename: Zaohuo
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Psychiatry, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, China.
authors.forename: Zhenhe
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Psychiatry, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Psychiatry, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Psychiatry, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Psychiatry, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, First Clinical Medical College/First Hospital of Shanxi Medical University, Taiyuan, China;
authors.forename: Kerang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, First Clinical Medical College/First Hospital of Shanxi Medical University, Taiyuan, China;
authors.forename: Sha
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, Institute of Mental Health, Sixth Hospital, Peking University, Beijing, China;
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Psychiatry, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, China zhangfq@njmu.edu.cn.
authors.forename: Fuquan
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000328:Adult; D051766:Early Growth Response Protein 1 / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D047908:Intracellular Signaling Peptides and Proteins; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C060615:SKIL protein, human; D014157:Transcription Factors
keywords: EGRl; miR-124-3p; microRNA; schizophrenia; transcriptional factor