乙肝病毒(HBV)感染对肝细胞癌(HCC)患者A-to-I RNA编辑的影响

Effects of hepatitis B virus (HBV) infection on A-to-I RNA editing in patients with hepatocellular carcinoma (HCC)

目的探究乙肝病毒(hepatitis B virus,HBV)感染对肝细胞癌(hepatocellular carcinoma,HCC)患者肝脏正常组织和癌组织中腺嘌呤转变为次黄嘌呤(adenine to inosine,A-to-I)RNA编辑活性的影响。方法从基因表达数据库(gene expression omnibus,GEO)收集28套成对正常组织和癌组织的转录组数据,分为HBV阴性正常组织(HBV-N)组、HBV阴性癌组织(HBV-T)组、HBV阳性正常组织(HBV+N)组和HBV阳性癌组织(HBV+T)组。用SPRINT软件进行位点鉴定后,从催化酶表达水平、位点编辑水平和位点所在基因的基因本体论(gene ontology,GO)富集通路层面进行分析。结果在正常组织和癌组织中均发现HBV感染时腺苷酸脱氨酶1(adenosine deaminases acting on RNA 1,ADAR1)表达水平更高。癌组织中HBV阳性样本的A-to-I RNA编辑水平上升,正常组织中则无此现象。两类组织中HBV阳性样本编辑基因显著富集在细胞增殖、基因调控相关信号通路。结论HBV感染上调ADAR1的表达,从而改变宿主编辑事件活性,这对HCC的发生发展可能有促进作用。

Objective To explore the effect of hepatitis B virus(HBV)infection on the activity of adenine to inosine(A-to-I)RNA editing events in normal and tumor liver tissues of patients with hepatocellular carcinoma(HCC).Methods We collected transcriptome sequencing data of 28 pairs of HCC normal and tumor liver tissues from gene expression omnibus(GEO)database.These samples were divided into HBV negative and normal liver tissues(HBV-N)group,HBV negative and tumor liver tissues(HBV-T)group,HBV positive and normal liver tissues(HBV+N)group and HBV positive and tumor liver tissues(HBV+T)group.Using a pipeline called SPRINT,we identified RNA editing sites and then analyzed them from expression level of catalytic enzyme,editing level of sites and gene ontology(GO)enrichment pathway of editing genes.Results Adenosine deaminases acting on RNA 1(ADAR1)was expressed at a higher level under HBV infection in both normal and tumor liver tissues.Editing level of A-to-I RNA editing sites increased under HBV infection in tumor samples,while there was no similar phenomenon in normal samples.The editing genes in HBV positive samples were significantly enriched in cell proliferation and gene regulation signaling pathways in the two types of tissues.Conclusions HBV infection up-regulates the expression of ADAR1 and changes the activity of host editing events,which may promote the development of HCC,and its intrinsic molecular mechanism remains to be studied.