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首页> 外文期刊>EBioMedicine >MicroRNA-137 Inhibits EFNB2 Expression Affected by a Genetic Variant and Is Expressed Aberrantly in Peripheral Blood of Schizophrenia Patients
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MicroRNA-137 Inhibits EFNB2 Expression Affected by a Genetic Variant and Is Expressed Aberrantly in Peripheral Blood of Schizophrenia Patients

机译:MicroRNA-137抑制遗传变异影响的EFNB2表达,并在精神分裂症患者的外周血中异常表达

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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.
机译:MicroRNA(miRNA)是一类约22个核苷酸的内源性和非编码单链RNA,其中许多在进化上是保守的。全基因组关联研究已经确定了欧洲人MIR137基因与精神分裂症之间的稳固统计关联,该研究在病例对照研究中在汉族人群中得以复制。在先前的研究中,我们提供了证据,证明汉族人群中EFNB2基因与精神分裂症之间存在显着关联。在当前的研究中,我们利用计算分析,点突变的载体构建,荧光素酶报告基因分析和包括RT-qPCR和Western blotting方法在内的基因表达分析研究了直接靶向EFNB2基因的miR-137,并探讨了该基因的遗传变异的逆转作用。 EFNB2 3'-UTR的推定种子对区域中的SNP rs550067317。我们还发现,在一组首次发作的精神分裂症患者和健康对照组的外周血中可以检测到miR-137,曲线下面积为0.795(95%置信区间0.700-0.890),这是中等诊断值疾病,表明它对于诊断精神分裂症可能有价值。总之,这项研究将增进我们对miR-137在精神分裂症相关信号通路中的作用的了解,并确定rs550067317精神分裂症的遗传基础。此外,我们为miR-137参与精神分裂症的病因和诊断提供了新的证据,这可能有助于发现该疾病的新生物标志物和治疗靶标。

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