基于生物信息学分析乙酰辅酶A酰基转移酶1在肾透明细胞癌中的表达及作用机制

Expression and activity mechanism of acetyl-CoA acyltransferase 1 in clear cell renal cell carcinoma based on bioinformatics

目的探讨乙酰辅酶A酰基转移酶1(ACAA1)在肾透明细胞癌(ccRCC)中的表达及作用机制。方法基于GEO数据集(GSE36895、GSE66272、GSE53737)、TCGA-KIRC数据集和Human Protein Atlas数据库分析ACAA1在正常肾组织和ccRCC组织中的表达。经Ualcan数据库进行ACAA1 mRNA与ccRCC临床病理特征的相关性分析。通过GEPIA数据库分析ACAA1 mRNA表达与ccRCC患者的预后关系。此外,利用STRING和Metascape数据库分别进行ACAA1蛋白互作网络构建及其功能机制探索。最后,通过mirDIP和DIANA-TarBase v8数据库预测调控ACAA1的潜在miRNA。结果与正常肾组织相比,ACAA1在ccRCC组织中显著低表达,且ACAA1 mRNA表达与ccRCC临床分期及组织学分级呈负相关。生存分析显示,ACAA1低表达的患者总体生存率以及无病生存率明显低于高表达患者。此外,通过STRING数据库构建了ACAA1蛋白互作网络,功能分析显示ACAA1及其相关基因主要参与脂肪酸β-氧化、脂肪酸代谢、线粒体β-饱和脂肪酸的氧化、过氧化物酶体蛋白转运、脂质代谢过程的调节和类固醇代谢过程等途径。最后,hsa-miR-25-3p和hsa-miR-363-3p可能通过靶向调节ACAA1进而影响ccRCC发生发展。结论ACAA1在ccRCC中低表达,并与其发生发展相关,为深入研究ACAA1在ccRCC中的作用机制提供理论帮助。

Objective To explore the expression of acetyl-CoA acyltransferase 1(ACAA1)in clear cell renal cell carcinoma(ccRCC)and investigate the correlative mechanism.Methods The GEO datasets(GSE36895,GSE66272,GSE53737),TCGA-KIRC dataset and Human Protein Atlas database were used to analyze the expression of ACAA1 in normal renal and ccRCC samples.Ualcan database was applied to analyze the correlation between ACAA1 mRNA and clinicopathological characteristics of ccRCC patients.The relationship between the ACAA1 mRNA levels and prognosis of ccRCC patients was determined using GEPIA database.Additionally,STRING and Metascape databases were used to construct a functional protein interaction network of ACAA1 and investigate its functional mechanism.Finally,the potential miRNAs that regulated ACAA1 were predicted by mirDIP and DIANA-TarBase v8 databases.Results ACAA1 expression level in ccRCC tissues was significantly lower than that in normal renal tissues,and ACAA1 mRNA expression was negatively correlated with the clinical stage and histological grade of ccRCC.Survival analysis showed that patients with low ACAA1 expression levels had significantly lower overall survival rate and disease-free survival rate than those with high ACAA1 expression levels.In addition,the ACAA1 protein interaction network was constructed through the STRING database and functional analysis showed that ACAA1 and its related genes were mainly involved in fatty acidβ-oxidation,fatty acid metabolism,mitochondrialβ-saturated fatty acid oxidation,peroxisomal protein transport,lipid regulation of metabolic processes and steroid metabolic processes.Finally,hsa-miR-25-3p and hsa-miR-363-3p might affect the occurrence and development of ccRCC by targeting ACAA1.Conclusion ACAA1 is down-expressed in ccRCC and related to its occurrence and development,which may provide theoretical assistance for in-depth study of the mechanism of ACAA1 in ccRCC.