肝癌模型小鼠中线粒体源外泌体基因的差异性表达分析

Analysis of differential expression of mitochondrion-derived exosomal genes in hepatocellular carcinoma model mice

目的探讨线粒体源外泌体基因参与肝细胞癌(HCC)病理过程的可能分子机制。方法通过RNA-seq和生物信息学手段,分析HCC中差异表达的线粒体源外泌体基因(DEMEs)及其生物学功能。结果HCC组织中共鉴定出93个DEMEs,其中74个表达下调,19个表达上调。表达下调的DEMEs经功能富集,共富集到4个生物学过程(biological process,BP)、4个细胞组分(cellular component,CC)、2个分子活性(molecular function,MF)、1个信号通路(KEGG pathway,KG)和4个蛋白位点序列特征(UP_SEQ_FEATURE,US)。它们参与了氧化还原、脂质代谢等过程,且大量DEMEs还具有线粒体转运肽功能。而上调表达的DEMEs,除了富集到1个CC,即线粒体组分,还发现其中一些参与了跨膜转运、对过氧化氢和对机械刺激的反应过程,有些还具有转移酶活性和ATP结合能力,并参与癌症的发生和转移等病理过程。结论线粒体源外泌体基因在HCC肿瘤组织与非肿瘤组织存在差异性表达,生物信息学分析显示这种差异性表达的基因涉及多个生物学过程,提示它们可能通过多种途径影响HCC的发生。

Objective To investigate the possible molecular mechanism of mitochondrion-derived exosomal exosome genes(DEMEs) involved in the pathological process of hepatocellular carcinoma(HCC).Methods The DEMEs in HCC and their biological functions were analyzed by RNA-seq and bioinformatics methods.Results 93 DEMEs were identified in HCC,among which 74 were down-regulated and 19 were upregulated.The down-regulated DEMEs were functionally enriched to 4 biological processes(BPs),4 cellular components(CCs),2 molecular functions(MFs),1 signal pathway(KG) and 4 UP-Seq features(USs).They involved in redox and lipid metabolism and majority of DEMEs had mitochondrial transport peptide-encoding sequences.The up-regulated DEMEs,in addition to the enrichment of 1 CC,i.e.mitochondrial component,were also found to be involved in the transmembrane transport,the reaction to hydrogen peroxide and mechanical stimulation,some of them also had transferase activity and the ATP binding ability,and involved in the occurrence and metastasis of cancer and other pathological processes.Conclusion Mitochondrion-derived exosomal genes are differentially expressed in HCC tumor and non-tumor tissues.Bioinformatics analysis shows that the DEMEs are involved many biological processes,suggesting that they may affect the development of HCC in various ways.