miRNAs在小鼠糖尿病肝病模型中的作用及其机制

The role and mechanism of miRNA in STZ-induced mouse diabetic hepatopathy

目的通过生物信息学方法探讨miRNAs在糖尿病肝病病变过程中的可能作用机制。方法首先从GEO数据库中采集链脲佐菌素(STZ)诱导糖尿病小鼠模型和同系小鼠正常肝组织中的miRNAs和mRNAs芯片检测的子数据集,并利用数据库信息与生物信息学分析,寻找与糖尿病肝病相关的miRNAs及所调控的靶向mRNAs。并通过20只STZ诱导糖尿病昆明小鼠和10只正常同系小鼠肝组织进行qRT-PCR检测验证。结果分析后获得差异表达显著的miRNAs,其中上调96个,下调77个;运用GO和KEGG的富集分析,结合数据库和参考文献的相关蛋白质注释,筛选出了可能与小鼠糖尿病肝病病变过程相关的miRNAs和效应mRNAs;实验小鼠肝组织的qRT-PCR检测发现,糖尿病肝组织中候选miR-34a-5p、miR-22-5p和miR-6998-5p的表达呈显著上调,而miR-200a-3p、miR-200b-3p和miR-222-3p的表达呈显著下调;另外,与之相关的Cers6、Mybl1、Scd2、Slco1a4和Plk2效应基因的表达呈上调趋势,而Acss2、Bcl6和Slc10a2效应基因的表达则呈下调趋势。结论这些候选miRNAs在小鼠糖尿病肝组织中的变化趋势与生物信息学预测研究相符,提示其在疾病过程中发挥着潜在的分子调控作用。

Objective To reveal possible mechanisms of miRNA in diabetic hepatopathy through bioinformatics method.Methods Subset data of miRNA and their matched mRNAs in the liver of STZ-induced diabetic mice and the normal liver tissues of congenial mice by detecting on microarrays were collected from GEO database;information from the database and bioinformatics analysis were applied to mine a batch of miRNAs in diabetic hepatopathy and targeted mRNAs regulated.Then qRT-PCR was used to verify the expressions of miRNAs in diabetic liver from 20 STZ-treated Kunming mice and 10 normal homologous mice.Results Via detection and analysis,miRNAs differentially expressed(including 96 up-regulated and 77 down-regulated)were significantly obtained.Groups of miRNAs and their effectors(mRNAs)that may be related to the pathological process of diabetic liver disease in mice were screened by GO and KEGG enrichment analyses,combined with relevant protein annotations in the databases and references.The expressions of miR-200a-3p,miR-200b-3p and miR-222-3p in the mice’s liver tissue detected by qRT-PCR were significantly down-regulated.In addition,the expressions of related effector genes CERS6,MYBL1,SCD2,SLCO1A4 and PLK2 were up-regulated,while the expressions of ACSS2,BCL6 and SLC10A2 were down-regulated.Conclusion The variation trend of those candidate miRNAs in mouse diabetic liver compared with that in control livers was consistent with that of the previous studies and prediction,which revealed their potential molecular regulation in this disease process.