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鉴定 8 种 miRNA 作为非酒精性脂肪性肝病的生物标志物。

Identification of 8-miRNAs as biomarkers for nonalcoholic fatty liver disease.

机构信息

Department of Gastroenterology, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Digestive System Disease, Wuhan, China.

Department of Digestive, Petrochemical General Hospital of Lanzhou, Gansu, China.

出版信息

J Cell Physiol. 2019 Aug;234(10):17361-17369. doi: 10.1002/jcp.28356. Epub 2019 Feb 20.

Abstract

Nonalcoholic fatty liver disease (NAFLD) poses serious threats to humans. Several studies have studied the biomarkers associated with NAFLD; however, the results vary because of the differences in the sequencing platform, sample selection, and filter conditions. This study aimed to explore the key microRNAs (miRNAs) of NAFLD by a systematic bioinformatics analysis. A total of 10 qualified NAFLD miRNA data sets were selected through a literature review. Signature miRNAs were identified by overlap comparison. The target genes of miRNAs were predicted by TargetScan software and functional enrichment, and transcription factor (TF) binding analysis of target genes was carried out by the database for annotation, visualization, and integrated discovery and Tfacts database, respectively. A total of three upregulated miRNAs and five downregulated miRNAs were identified in the NAFLD tissue. The target genes of upregulated miRNAs mainly enriched in the RNA polymerase II promoter transcriptional regulation, chromatin remodeling process, and O-glycan synthesis, circadian rhythm, and endocytosis; the target genes of downregulated miRNAs mainly enriched in the transcriptional regulation of DNA as a template, negative regulation process of protein phosphorylation, and Fc epsilon RI signaling pathways, Ras signaling pathways and the interaction between cytokines and cytokines. Besides, 136 interactions were formed between 62 TFs and 45 target genes of upregulated miRNA, whereas 157 interactions were formed between 72 TFs and 45 target genes of downregulated miRNA. Both contained 102 TFs, and 32 TFs were present in both target genes. To summarize, we identified an eight-miRNA set as a signature for NAFLD, which will benefit the clinical treatment of NAFLD.

摘要

非酒精性脂肪性肝病 (NAFLD) 对人类健康构成严重威胁。已有多项研究探讨了与 NAFLD 相关的生物标志物,但由于测序平台、样本选择和过滤条件的差异,结果存在差异。本研究旨在通过系统的生物信息学分析来探索 NAFLD 的关键 microRNAs (miRNAs)。通过文献回顾,共筛选出 10 个合格的 NAFLD miRNA 数据集。通过重叠比较确定特征 miRNA。使用 TargetScan 软件预测 miRNA 的靶基因,并进行功能富集分析,分别使用数据库 for annotation, visualization, and integrated discovery 和 Tfacts 数据库进行靶基因转录因子 (TF) 结合分析。在 NAFLD 组织中鉴定出 3 个上调 miRNA 和 5 个下调 miRNA。上调 miRNA 的靶基因主要富集在 RNA 聚合酶 II 启动子转录调控、染色质重塑过程、O-聚糖合成、昼夜节律和内吞作用;下调 miRNA 的靶基因主要富集在 DNA 模板转录调控、蛋白质磷酸化的负调控过程、Fc epsilon RI 信号通路、Ras 信号通路和细胞因子与细胞因子的相互作用。此外,上调 miRNA 的 62 个 TF 和 45 个靶基因之间形成 136 个相互作用,下调 miRNA 的 72 个 TF 和 45 个靶基因之间形成 157 个相互作用。两者都包含 102 个 TF,在两个靶基因中都存在 32 个 TF。总之,我们确定了一个由 8 个 miRNA 组成的 NAFLD 特征signature,这将有助于 NAFLD 的临床治疗。

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