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基于调控网络的生物分析鉴定儿童哮喘相关差异表达基因。

Identification of differentially expressed genes associated with asthma in children based on the bioanalysis of the regulatory network.

机构信息

Department of Pediatrics, Shanghai Fengxian Fengcheng Hospital, Shanghai 200000, P.R. China.

Department of Pediatrics, Ren Ji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200000, P.R. China.

出版信息

Mol Med Rep. 2018 Aug;18(2):2153-2163. doi: 10.3892/mmr.2018.9205. Epub 2018 Jun 22.

Abstract

Asthma, the most common chronic respiratory tract disease in children, is characterized by allergy, recurring airway obstruction and bronchospasm. The aim of the present study was to screen critical differentially expressed genes (DEGs) involved in asthma in children. Gene expression in different tissues was compared between asthmatic children and healthy control subjects in order to identify DEGs associated with asthma. Protein‑protein interaction (PPI) networks were constructed for the DEGs and weighted gene co‑expression network analysis methods were used to further determine the functional modules associated with DEGs in different tissue samples. In addition, the gene co‑expression network was constructed. Gene Ontology function analysis and pathway analysis were conducted to identify critical DEGs. The results identified numerous DEGs from the different tissue samples, including 1,662 DEGs from nasal‑epithelium tissue samples, 572 DEGs from peripheral blood (PB) samples and 146 DEGs from PB mononuclear cells samples. In the PPI network, F‑box only protein 6 (FBXO6), histone deacetylase 1 (HDAC1) and amyloid β precursor protein (APP) were hub genes and served an important role in the process of asthma. In addition, proliferating cell nuclear antigen (PCNA), integrin α‑4 (ITGA4), catenin α‑1 (CTNNA1), nuclear factor‑κB1 (NF‑κB1) and mechanistic target of rapamycin (MTOR) may be critical DEGs involved in the progression of asthma in children. These results suggested that FBXO6, HDAC1 and APP may interact with PCNA, ITGA4, CTNNA1, NF‑κB1 and mTOR in the progression of asthma in children.

摘要

哮喘是儿童最常见的慢性呼吸道疾病,其特征为过敏、反复出现气道阻塞和支气管痉挛。本研究旨在筛选儿童哮喘中涉及的关键差异表达基因(DEG)。为了鉴定与哮喘相关的 DEG,比较了哮喘儿童和健康对照者不同组织中的基因表达。构建了 DEG 的蛋白质-蛋白质相互作用(PPI)网络,并使用加权基因共表达网络分析方法进一步确定不同组织样本中与 DEG 相关的功能模块。此外,构建了基因共表达网络。进行基因本体功能分析和通路分析,以鉴定关键 DEG。结果从不同组织样本中鉴定出大量 DEG,包括鼻上皮组织样本中的 1662 个 DEG、外周血(PB)样本中的 572 个 DEG 和 PB 单核细胞样本中的 146 个 DEG。在 PPI 网络中,F-框仅蛋白 6(FBXO6)、组蛋白去乙酰化酶 1(HDAC1)和淀粉样β前体蛋白(APP)是枢纽基因,在哮喘过程中发挥重要作用。此外,增殖细胞核抗原(PCNA)、整合素α-4(ITGA4)、连环蛋白α-1(CTNNA1)、核因子-κB1(NF-κB1)和雷帕霉素的机制靶点(MTOR)可能是儿童哮喘进展中的关键 DEG。这些结果表明,FBXO6、HDAC1 和 APP 可能与 PCNA、ITGA4、CTNNA1、NF-κB1 和 mTOR 相互作用,参与儿童哮喘的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b0f/6072229/25b6790cbb31/MMR-18-02-2153-g02.jpg

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