乙型肝炎相关慢加急性肝衰竭患者lncRNA表达谱分析

Analysis on lncRNA Expression Profile in Patients with HBVrelated Acute-on-chronic Liver Failure

为了分析乙型肝炎相关慢加急性肝衰竭(hepatitis B virus-related acute-on-chronic liver failure,HBVACLF)患者与乙肝携带者(asymptomatic carrier,ASC)间差异表达的长链非编码RNA(long non-coding RNA,lncRNA),探究lncRNA在HBV-ACLF中的功能,选取5例HBV-ACLF患者和5例ASC患者,应用高通量测序检测其外周血中lncRNA及信使RNA(messenger RNA,mRNA)的表达谱,筛选出在两组间差异表达的lncRNA及mRNA,并进一步对差异表达的lncRNA进行生物信息学分析。结果显示,与ASC组相比,HBV-ACLF组中共发现了131个异常表达的lncRNA,表达上调的lncRNA有114个,表达下调的lncRNA有17个,其中lncRNA PIGC上调最显著。GO分析表明,差异表达的lncRNA主要参与病毒复制、固有免疫、小分子物质代谢等生物学过程;KEGG分析发现,差异表达的lncRNA主要参与核黄素代谢、类固醇激素生物合成、果糖和甘露糖代谢、卟啉和叶绿素代谢、叶酸生物合成、氨基酸和核苷酸代谢等信号通路。Cis预测提示,lncRNA PIGC能调控mRNA ENST00000484368的表达。本研究筛选出了在HBV-ACLF患者中差异表达的lncRNA谱,并发现lncRNA很可能通过调节肝细胞的小分子代谢及肝脏免疫反应在HBV-ACLF中发挥作用。

To analyze differentially expressed long non-coding RNAs(lncRNAs)between patients with hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)and asymptomatic carrier(ASC),and explore the functions of lncRNAs in HBV-ACLF.Five patients with HBV-ACLF and 5 patients with ASC were selected respectively,and the expression profiles of lncRNAs and mRNAs in peripheral blood of these 10 patients were detected by high-throughput sequencing.The differentially expressed lncRNAs and mRNAs between the two groups were screened,and bioinformatic analysis was further conducted for the differentially expressed lncRNAs.The results showed that,compared with the ASC group,there were 131 differentially expressed lncRNAs in the HBV-ACLF group,including 114 up-regulated lncRNAs,and 17 down-regulated lncRNAs.Among them,lncRNA PIGC was the most significantly up-regulated.GO analysis showed that the differentially expressed lncRNAs were mainly involved in biological processes such as viral infection,innate immunity,small molecule metabolism,etc.KEGG analysis found that these lncRNAs were mainly involved in riboflavin metabolism,steroid hormone biosynthesis,fructose and mannose metabolism,porphyrin and chlorophyll metabolism,folate biosynthesis,amino acid and nucleotide metabolism and other signaling pathways.Cis prediction revealed that lncRNA PIGC could regulate the expression of mRNA ENST00000484368.This study confirmed the differential expression of lncRNAs in HBV-ACLF,and demonstrated that lncRNAs are likely to play a role in HBV-ACLF by regulating the small molecule metabolism in liver cells and liver immune response.