Microrna microarray analysis combined with interaction network analysis to investigate the influence of clozapine to metabolic syndrome.

Tianhua  Chen; Lin  Yang; Dengtang  Liu; Dong Hong  Cui; Shunying  Yu; Yan  Li; Haisu  Wu; Ying  Yue; Yifeng  Xu; Yongyong  Shi

Tianhua Chen Schizophrenia Program, Shanghai Mental Health Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Lin Yang Schizophrenia Program, Shanghai Mental Health Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Dengtang Liu Schizophrenia Program, Shanghai Mental Health Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Dong Hong Cui Schizophrenia Program, Shanghai Mental Health Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Shunying Yu Schizophrenia Program, Shanghai Mental Health Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Yan Li Shanghai Jiao Tong University, Shanghai, Shanghai Shi, China

Haisu Wu Schizophrenia Program, Shanghai Mental Health Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Ying Yue Shanghai Jiao Tong University, Shanghai, People`s Republic of China

Yifeng Xu Shanghai Luwan Mental Health Center, Shanghai, People`s Republic of China

Yongyong Shi Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes (Ministry of Education);Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong; Schizophrenia Program, Shanghai Mental Health Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

The Metabolic Syndrome (MetS) could significantly increase the risk of morbidity and mortality from type II diabetes and cardiovascular disease. We carried out a systemical study to investigate the potential drug targets for effective treatment of clozapine-induced MetS. In our study, the differentially-expressed miRNAs (DERs) between schizophrenia patients with MetS and without MetS after the treatment of clozapine were identified. Target genes of these miRNAs were then retrieved from two miRNA databases (miRecods and miRTarBase) to identify the underlying mechanisms involved in the development of MetS. Interactors of the target genes were identified and a network was constructed using Osprey. Functional enrichment analysis was performed for all the genes in the network with DAVID (Database for Annotation, Visualization and Integrated Discovery). The results revealed that 3 DERs including Hsa-miR-330-3p (p = 0.00934), has-miR-18 a (p = 0.001 686) and has-miR-1 06b (p = 0.007531)were identified. In total, 4 target genes (E2F1, CTGF, ESR1 and ITCH) shared by both databases were picked out. What`s more, 8 significant pathways were revealed in the interaction network and the most significant pathway was positive regulation of macromolecule metabolic process (FDR = 1.80E-15). In conclusion, the 3 identified miRNAs might be the potential targets for treatment of MetS. And the results of our study provide ways to monitor the progression of MetS (e.g., serum levels of proteins), predict the outcome (e.g., polymorphisms) and even block the emergence of MetS.