کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10225558 | 1701188 | 2018 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Schizophrenia-associated rs4702 G allele-specific downregulation of FURIN expression by miR-338-3p reduces BDNF production
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
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چکیده انگلیسی
Genome-wide association studies (GWAS) reveal numerous schizophrenia (SCZ)-associated single-nucleotide polymorphisms (SNPs); however, functional characterizations of the risk variants remain to be established. Using data from 108 SCZ GWAS loci, we performed systematic miRNA binding site screening of 128 SCZ-associated SNPs and found that 2 out of 3 SNPs located in the 3â²UTR were predicted to alter 3 miRNAs' binding sites in 2 target genes. Of the identified SNPs, the most genome-wide significant SNP rs4702 (A/G) in the FURIN 3â²UTR, previously identified as an SCZ-associated cis-expression quantitative trait loci (downregulated by the risk G allele), is located in the binding site of miR-338-3p in the presence of the risk G allele. Allele-specific downregulation of FURIN by miR-338-3p was validated with a luciferase reporter assay. Furthermore, we demonstrated that miR-338-3p-mediated FURIN inhibition reduced brain-derived neurotrophic factor (BDNF) maturation and secretion in human embryonic kidney 293T cells. Our data reveal that schizophrenia-associated rs4702 G allele-specific downregulation of FURIN by miR-338-3p reduces mature BDNF production. These data help elucidate the mechanism of genetic predisposition toward schizophrenia or other neurodevelopmental diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Schizophrenia Research - Volume 199, September 2018, Pages 176-180
Journal: Schizophrenia Research - Volume 199, September 2018, Pages 176-180
نویسندگان
Yu Hou, Wenquan Liang, Jian Zhang, Qiyang Li, Haiyan Ou, Zhongju Wang, Shufen Li, Xingbing Huang, Cunyou Zhao,