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基于生物信息学分析鉴定非酒精性脂肪性肝病进展中的关键基因。

Identification of key genes in non‑alcoholic fatty liver disease progression based on bioinformatics analysis.

机构信息

Department of Liver Disease, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, P.R. China.

Department of Infectious Disease, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, P.R. China.

出版信息

Mol Med Rep. 2018 Jun;17(6):7708-7720. doi: 10.3892/mmr.2018.8852. Epub 2018 Apr 5.

Abstract

Due to economic development and lifestyle changes, the incidence of non‑alcoholic fatty liver disease (NAFLD) has gradually increased in recent years. However, the pathogenesis of NAFLD is not yet fully understood. To identify candidate genes that contribute to the development and progression of NAFLD, two microarray datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified and functional enrichment analyses were performed. A protein‑protein interaction network was constructed and modules were extracted using the Search Tool for the Retrieval of Interacting Genes and Cytoscape. The enriched functions and pathways of the DEGs included 'cellular macromolecule biosynthetic process', 'cellular response to chemical stimulus', 'extracellular matrix organization', 'metabolic pathways', 'insulin resistance' and 'forkhead box protein O1 signaling pathway'. The DEGs, including type‑1 angiotensin II receptor, formin‑binding protein 1‑like, RNA‑binding protein with serine‑rich domain 1, Ras‑related C3 botulinum toxin substrate 1 and polyubiquitin‑C, were identified using multiple bioinformatics methods and validated in vitro with reverse transcription‑quantitative polymerase chain reaction analysis. In conclusion, five hub genes were identified in the present study, and they may aid in understanding of the molecular mechanisms underlying the development and progression of NAFLD.

摘要

由于经济发展和生活方式的改变,近年来非酒精性脂肪性肝病(NAFLD)的发病率逐渐升高。然而,NAFLD 的发病机制尚不完全清楚。为了鉴定参与 NAFLD 发生和进展的候选基因,从基因表达综合数据库中下载了两个微阵列数据集。鉴定差异表达基因(DEGs)并进行功能富集分析。使用 Search Tool for the Retrieval of Interacting Genes 和 Cytoscape 构建蛋白质-蛋白质相互作用网络并提取模块。DEGs 的富集功能和途径包括“细胞大分子生物合成过程”、“细胞对化学刺激的反应”、“细胞外基质组织”、“代谢途径”、“胰岛素抵抗”和“叉头框蛋白 O1 信号通路”。使用多种生物信息学方法鉴定包括 1 型血管紧张素 II 受体、formin 结合蛋白 1 样、富含丝氨酸的 RNA 结合蛋白 1、Ras 相关 C3 肉毒杆菌毒素底物 1 和多聚泛素-C 在内的 DEGs,并通过逆转录-定量聚合酶链反应分析进行了体外验证。总之,本研究鉴定了五个枢纽基因,它们可能有助于理解 NAFLD 发生和进展的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d16e/5983972/82bb14c5fd12/MMR-17-06-7708-g00.jpg

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