海南医科大学学报2025，Vol.31Issue(18)：1379-1389,11.DOI:10.13210/j.cnki.jhmu.20241017.001
溃疡性结肠炎中风险miRNA的内质网应激相关特征基因鉴定和分析
Identification and analysis of endoplasmic reticulum stress-related characteristics of risk miRNAs in ulcerative colitis
摘要
Abstract
Objective:To identify risk miRNAs in ulcerative colitis(UC)by using Mendelian randomization(MR)and bioin-formatics analysis and to identify the immunopathological mechanisms that target key genes in endoplasmic reticulum stress(ERS),thereby finding the effective biomarkers for the diagnosis and treatment of UC and providing new directions for its studies.Methods:miRNA exposure data and UC outcome data sets from a genome-wide association study database were used to identify causal risk miRNAs in UC by MR analysis.Next,multiple UC microarray data sets were extracted using gene expression database for difference analysis,and the risk miRNA-targeted ERS related genes were intersected,and the selected genes were identified by machine learning methods to identify their characteristic key genes.Then,the biological function prediction and immune infiltra-tion evaluation of key genes were performed.Finally,the expression of key genes was verified by an independent chip dataset.Re-sults:MR analysis identified a causal relationship between hsa-miR-130b-3p as a protective factor and UC.Subsequently,differen-tial genes were analyzed through the combined data of UC multi-chip and intersected with ERS related genes targeted by miRNA.Five intersection genes were selected as XBP1,PPARG,LRRK2,MAP3K5,and EDN1.Then,two machine learning methods were used to identify these five intersection genes as key UC characteristic genes,and single gene enrichment and immune infiltra-tion were used to analyze whether these key genes play a role through immune regulatory networks and intestinal immune cells.Fi-nally,the independent chip dataset was verified again.In UC,the expressions of EDN1 and PPARG were down-regulated,while the expressions of XBP1,LRRK2,and MAP3K5 were up-regulated.Conclusion:hsa-miR-130b-3p is a risk miRNA for UC,and its targeted regulation of key ER stress genes XBP1,PPARG,LRRK2,MAP3K5,and EDN1 are of great significance as di-agnostic biomarkers of the disease,and their potential biological pathways and immune correlations provide new insights into the pathogenesis of UC.关键词
溃疡性结肠炎/microRNA/内质网应激/孟德尔随机化/生物信息学/关键基因Key words
Ulcerative colitis/microRNA/Endoplasmic reticulum stress/Mendelian randomization/Bioinformatics/Key genes分类
医药卫生引用本文复制引用
陈旭永,杨小红,王柳丹,吴海东,郭一凡,苗新普..溃疡性结肠炎中风险miRNA的内质网应激相关特征基因鉴定和分析[J].海南医科大学学报,2025,31(18):1379-1389,11.基金项目
This study was supported by the National Natural Science Foundation of China(82160104) 国家自然科学基金资助项目(82160104) （82160104）
