title: MicroRNA-137 Inhibits EFNB2 Expression Affected by a Genetic Variant and Is Expressed Aberrantly in Peripheral Blood of Schizophrenia Patients.
abstract: MicroRNAs (miRNAs) are a class of endogenous and non-coding single-stranded RNAs of approximately 22 nucleotides, many of which are evolutionarily conserved. Genome-wide association studies have identified a robust statistical association between the MIR137 gene and schizophrenia in Europeans, which was replicated in the Han Chinese population in a case-control study. In the previous study, we provided evidence for a significant association between the EFNB2 gene and schizophrenia in Han Chinese subjects. In the current study, we utilized computational analysis, vector construction of point mutations, luciferase reporter assays and gene expression assays including RT-qPCR and western blotting methods to investigate miR-137 directly targeting EFNB2 gene and explore the reversal effect of a genetic variant of SNP rs550067317 in the putative seed-pair region of EFNB2 3'-UTR. We also found that miR-137 could be detected in the peripheral blood of a cohort of first-onset schizophrenia patients and healthy controls, and the area under curve was 0.795 (95% confidence interval 0.700-0.890), which is a middle diagnostic value for disease, suggesting that it might be valuable for diagnosing schizophrenia. In summary, this study would improve our understanding of the role of miR-137 in schizophrenia-associated signaling pathways and identify the genetic basis of rs550067317 for schizophrenia. Furthermore, we provided new evidence for the involvement of miR-137 in the etiology and diagnosis of schizophrenia, which might contribute to the discovery of new biomarkers and therapeutic targets for the disease.
authors.affiliation: Department of Biochemistry and Molecular Biology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, China; Translational medicine center, Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710054, China. Electronic address: zhangruity12@163.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, China.
authors.forename: Fayi
authors.initials: F
authors.lastname: Nie
authors.affiliation: Department of Biochemistry and Molecular Biology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, China.
authors.forename: Congshan
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Biochemistry and Molecular Biology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Human Genetics 4, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Valenzuela
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Liu
authors.affiliation: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Biochemistry and Molecular Biology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, China. Electronic address: majie_article@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
mesh_terms: D020413:3' Untranslated Regions; D000483:Alleles; D001483:Base Sequence; D002460:Cell Line; D019295:Computational Biology / Q000379:methods; D030561:Databases, Nucleic Acid; D036388:Ephrin-B2 / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D009690:Nucleic Acid Conformation; D020641:Polymorphism, Single Nucleotide; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C000601239:EFNB2 protein, human; D036388:Ephrin-B2; C545567:MIRN137 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: EFNB2; MiR-137; Regulation; SNP; Schizophrenia