山西医科大学学报2024，Vol.55Issue(10)：1288-1294,7.DOI:10.13753/j.issn.1007-6611.2024.10.005
基于RNA-seq分析TBL2基因在心肌细胞缺氧/复氧损伤中的作用机制
Role and mechanism of TBL2 gene in hypoxia/reoxygenation injury of cardiomyocytes based on RNA-seq analysis
摘要
Abstract
Objective To investigate the effects of transducin β-like protein 2(TBL2)gene on hypoxia/reoxygenation(H/R)injury in rat myocardial H9c2 cells by transcriptome sequencing technology.Methods The cardiomyocyte injury model was established in H9c2 cells through H/R induction to simulate myocardial ischemia in vitro.The expression level of TBL2 in H/R cardiomyocytes and normal H9c2 cells was detected by Western blot.H9c2 cardiomyocytes were transfected with TBL2-siRNA(si-TBL2 group)and NC-siRNA(si-NC group),respectively,and then subjected to H/R treatment.Three samples were taken from each group for RNA-seq.The differentially expressed genes(DEGs)were screened by DESeq2 software.The GO and KEGG functional annotation and enrich-ment analysis of DEGs were conducted using ClusterProfiler.The protein-protein interaction(PPI)network of DEGs was established using the STRING database in combination with Cytoscape software,and the core genes were screened.Results Compared with normal H9c2 cells,TBL2 was significantly elevated in H/R cardiomyocytes(P=0.002 2).Transcriptome sequencing analysis identified a total of 905 differentially expressed genes(DEGs)between si-TBL2 group and si-NC group,among which 566 were downregulated and 309 were upregulated.GO functional enrichment analysis indicated that the DEGs were mainly enriched in biological processes such as cell adhesion,regulation of systemic arterial blood pressure,and potassium ion transport,cellular components such as extra-cellular matrix,extracellular space,and protein complexes involved in cell adhesion,and molecular functions such as transmembrane receptor activity,signal receptor activity,inorganic cation transmembrane transporter activity,and G protein-coupled receptor activity.KEGG pathway enrichment analysis demonstrated that the DEGs were mainly distributed in 40 signaling pathways,mainly including cell adhesion molecules,neuroactive ligand-receptor interactions,ECM receptor interactions,PI3K/Akt signaling pathway,calcium signaling pathway,protein digestion and absorption,etc.Through the construction of the PPI network diagram,a total of 7 core genes were screened out,including IL-6,LEP,IL-1α,FGF9,GFAP,CD68,and AGT.Conclusion TBL2 is significantly highly expressed in the myocardial infarction cell model.There are remarkable differentially expressed genes in the H/R-induced H9c2 cardiomyocyte injury model after inhibiting TBL2 gene.TBL2 participates in the regulation of multiple biological processes and signaling pathways,affects the processes of proliferation,apoptosis,and inflammatory response of cardiomyocytes.TBL2 may potentially be a therapeutic target for myocardial infarction.关键词
TBL2/急性心肌梗死/转录组测序/生物信息学分析/H9c2心肌细胞/治疗靶点Key words
TBL2/acute myocardial infarction/transcriptome sequencing/bioinformatics analysis/H9c2 cardiomyo-cytes/therapeutic targets分类
医药卫生引用本文复制引用
郭晨媛,韩昭迪,刘嘉欣,张逸飞,杨五小..基于RNA-seq分析TBL2基因在心肌细胞缺氧/复氧损伤中的作用机制[J].山西医科大学学报,2024,55(10):1288-1294,7.基金项目
山西省科技厅自然科学研究面上基金资助项目(202103021224373) （202103021224373）
