肥胖基因及其互作microRNA与疾病发生关联的生物信息学研究

Bioinformatics Studies on the Association between Obesity Genes and Their Interacting microRNAs with Disease Occurrence

摘要: 目的：基于生物信息学探讨肥胖与疾病发生的关联。方法：分别以“肥胖”、“心血管疾病”、“心脏病”、“癌症”、“肝脏代谢失调”为关键词，在相关疾病数据库(Genecards、TTD、OMIM、Uniprot)中获取关键靶点。基于STRING数据库构建疾病与肥胖交叉靶点的蛋白–蛋白互作网络，筛选核心作用靶点，利用DAVID数据库进行基因本体功能(GO)以及京都基因与基因组百科全书(KEGG)通路富集分析，预测作用在核心作用靶点上的非编码RNA、转录因子，并构建基因调控网络。结果：筛选肥胖与心血管疾病的核心作用靶点25个，互作miRNA 58个；肥胖与心脏病核心作用靶点30个，互作miRNA 81个；肥胖与癌症核心作用靶点25个，互作miRNA 84个；肥胖与肝脏代谢失调核心作用靶点30个，互作miRNA 73个。肥胖与心血管疾病核心作用靶点主要富集于脂质和动脉粥样硬化、腺苷酸激活蛋白激酶信号通路等；肥胖与心脏病核心作用靶点主要富集于胆固醇代谢、脂质动脉粥样硬化等信号通路；肥胖与癌症核心作用靶点主要富集于腺苷酸激活蛋白激酶、磷脂酰肌醇3–激酶–Akt信号通路等；肥胖与肝脏代谢失调的核心作用靶点主要富集于非酒精性脂肪性肝病、脂肪细胞因子信号通路等。本研究为后续探究肥胖与疾病间复杂的作用关系提供了新方向与新思路。

Abstract: Objective: To explore the association between obesity and disease occurrence based on bioinformatics. Methods: The key targets were obtained from the related disease databases (Genecards, TTD, OMIM, Uniprot) with the keywords of “obesity”, “cardiovascular disease”, “heart disease”, “cancer” and “liver metabolic disorder”. Based on the STRING database, the protein-protein interaction network of disease and obesity cross-targets was constructed, the core targets were screened, and the DAVID database was used to analyze the gene ontology function (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, so as to predict the non-coding RNA and transcription factors acting on the core targets, and construct the gene regulatory network. Results: A total of 25 core targets and 58 interacting miRNAs were screened between obesity and cardiovascular diseases. There were 30 core targets of obesity and heart disease, and 81 interacting miRNAs. There were 25 core targets of obesity and cancer, and 84 interacting miRNAs. There were 30 core targets of obesity and liver metabolic disorders, and 73 interacting miRNAs. The core targets of obesity and cardiovascular disease are mainly enriched in lipids, atherosclerosis, adenylate-activated protein kinases, the signaling pathway, etc. The core targets of obesity and heart disease are mainly enriched in cholesterol metabolism, lipid atherosclerosis and other signaling pathways. The core targets of obesity and cancer are mainly enriched in adenylate-activated protein kinase and phosphatidylinositol 3-kinase-Akt signaling pathway. The core targets of obesity and liver metabolic disorders are mainly enriched in non-alcoholic fatty liver disease and adipocytokine signaling pathways. This study provides a new direction and new ideas for the follow-up exploration of the complex relationship between obesity and disease.