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长非编码 RNA 相关竞争性内源性 RNA 轴在精神分裂症嗅上皮中的作用:一项生物信息学分析。

Long non-coding RNA-associated competing endogenous RNA axes in the olfactory epithelium in schizophrenia: a bioinformatics analysis.

机构信息

Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Sci Rep. 2021 Dec 30;11(1):24497. doi: 10.1038/s41598-021-04326-0.

Abstract

The etiology of schizophrenia (SCZ), as a serious mental illness, is unknown. The significance of genetics in SCZ pathophysiology is yet unknown, and newly identified mechanisms involved in the regulation of gene transcription may be helpful in determining how these changes affect SCZ development and progression. In the current work, we used a bioinformatics approach to describe the role of long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) in the olfactory epithelium (OE) samples in order to better understand the molecular regulatory processes implicated in SCZ disorders in living individuals. The Gene Expression Omnibus database was used to obtain the OE microarray dataset (GSE73129) from SCZ sufferers and control subjects, which contained information about both lncRNAs and mRNAs. The limma package of R software was used to identify the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs). RNA interaction pairs were discovered using the Human MicroRNA Disease Database, DIANA-LncBase, and miRTarBase databases. In this study, the Pearson correlation coefficient was utilized to find positive correlations between DEmRNAs and DElncRNAs in the ceRNA network. Eventually, lncRNA-associated ceRNA axes were developed based on co-expression relations and DElncRNA-miRNA-DEmRNA interactions. This work found six potential DElncRNA-miRNA-DEmRNA loops in SCZ pathogenesis, including, SNTG2-AS1/hsa-miR-7-5p/SLC7A5, FLG-AS1/hsa-miR-34a-5p/FOSL1, LINC00960/hsa-miR-34a-5p/FOSL1, AQP4-AS1/hsa-miR-335-5p/FMN2, SOX2-OT/hsa-miR-24-3p/NOS3, and CASC2/hsa-miR-24-3p/NOS3. According to the findings, ceRNAs in OE might be promising research targets for studying SCZ molecular mechanisms. This could be a great opportunity to examine different aspects of neurodevelopment that may have been hampered early in SCZ patients.

摘要

精神分裂症(SCZ)作为一种严重的精神疾病,其病因尚不清楚。遗传在 SCZ 病理生理学中的意义尚不清楚,而新发现的参与基因转录调控的机制可能有助于确定这些变化如何影响 SCZ 的发展和进程。在目前的工作中,我们使用生物信息学方法描述了长非编码 RNA(lncRNA)相关竞争性内源 RNA(ceRNA)在嗅觉上皮(OE)样本中的作用,以便更好地了解涉及 SCZ 个体中分子调控过程。我们从 SCZ 患者和对照者中获得了 OE 微阵列数据集(GSE73129),该数据集包含 lncRNA 和 mRNA 的信息。使用 R 软件的 limma 包来识别差异表达的 lncRNA(DElncRNA)和 mRNAs(DEmRNAs)。使用 Human MicroRNA Disease Database、DIANA-LncBase 和 miRTarBase 数据库发现 RNA 相互作用对。在这项研究中,Pearson 相关系数用于在 ceRNA 网络中发现 DEmRNAs 和 DElncRNAs 之间的正相关关系。最终,根据共表达关系和 DElncRNA-miRNA-DEmRNA 相互作用,开发了 lncRNA 相关的 ceRNA 轴。这项工作在 SCZ 发病机制中发现了六个潜在的 DElncRNA-miRNA-DEmRNA 循环,包括 SNTG2-AS1/hsa-miR-7-5p/SLC7A5、FLG-AS1/hsa-miR-34a-5p/FOSL1、LINC00960/hsa-miR-34a-5p/FOSL1、AQP4-AS1/hsa-miR-335-5p/FMN2、SOX2-OT/hsa-miR-24-3p/NOS3 和 CASC2/hsa-miR-24-3p/NOS3。根据这些发现,OE 中的 ceRNAs 可能是研究 SCZ 分子机制的有前途的研究靶点。这可能是一个很好的机会,可以研究 SCZ 患者早期可能受到阻碍的不同神经发育方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccdc/8718521/3fb39e78dabf/41598_2021_4326_Fig1_HTML.jpg

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