HIV-1感染长期不进展者外周血单个核细胞中的环状RNA表达谱  

Circular RNA expression profile of peripheral blood mononuclear cells in long-term non-progressors infected with HIV-1

作　　者：廖银璐 易春杏 陈秀 覃彤雪 陶婞 李金苗 黄有金 韦雯菲 陈荣凤[1,2] 蒋俊俊 Liao Yinlu;Yi Chunxing;Chen Xiu;Qin Tongxue;Tao Xing;Li Jinmiao;Huang Youjin;Wei Wenfei;Chen Rongfeng;Jiang Junjun(School of Public Health,Guangxi Medical University,Nanning 530021,China;Key Laboratory of AIDS Prevention and Control Research in Guangxi,Nanning 530021,China)

机构地区：[1]广西医科大学公共卫生学院,南宁530021 [2]广西艾滋病防治研究重点实验室,南宁530021

出　　处：《广西医科大学学报》2022年第12期1883-1890,共8页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.81703275,No.81960602);广西杰出青年科学基金(No.2018GXNSFFA281001)。

摘　　要：目的:了解HIV-1感染的长期不进展者(LTNP)和典型进展者(TP)外周血单个核细胞(PBMC)中的环状RNA(circRNA)表达谱,探究circRNA对HIV-1感染发病机制的潜在作用。方法:分别采集3例LTNP和TP的血液样本,分离PBMCs进行circRNA测序,通过edgeR鉴定差异表达的circRNA,并对这些差异表达的circRNA亲本基因进行GO和KEGG功能分析。使用生物信息学工具构建circRNA-miRNA-mRNA相互作用网络,并利用外部数据对下游调控的基因进行验证。结果:两组共鉴定出155个差异表达的circRNA,LTNP中大多数circRNA表达下调。GO和KEGG富集分析显示,20种途径可能与HIV-1感染长期非进展有关,包括自然杀伤细胞介导的细胞毒性途径。circRNA-miRNA-mRNA相互作用网络包括14个circRNA,17个miRNA和129个mRNA,另一个数据集验证了下游15个mRNA的差异表达,可能被circRNA调控的基因主要包括FOXP4、GP6、C9orf116等。在circRNA-miRNA-mRNA互作网络中,circRNA_chr1:39804878|39808198和circRNA_chr18:44701174|44703102可能通过充当miRNA海绵调节其靶基因NUML和Cav-1的表达影响HIV疾病进展。结论:与TP相比,LTNP的PBMC中大多数circRNA表达下调,circRNA亲本基因主要富集在与HIV感染相关的炎症和免疫途径上;circRNA还可以通过充当miRNA的海绵参与HIV疾病进展的调节,这为研究HIV疾病进展的机制提供了新的方向。Objective:To understand the circRNA expression profile of peripheral blood mononuclear cells(PBMC)in long term non-progressors(LTNPs)and typical progressors(TPs)infected with HIV-1,and to explore the potential role of circRNA on the pathogenesis of HIV-1 infection.Methods:Three LTNP and TP blood samples were collected,PBMCs were isolated for circRNA sequencing,and differentially expressed circRNAs were identified by edgeR.GO and KEGG functional analyses were performed on the differentially expressed circRNA parent genes.In addition,bioinformatics tools were used to construct a circRNA-miRNA-mRNA interaction network and external data were used to verify downstream regulated genes.Results:A total of 155 differentially expressed circRNAs were identified in both groups,and most of the circRNA expressions in LTNPs were down-regulated.GO and KEGG enrichment analyses revealed that 20 pathways might have a correlation with long-term non progression of HIV-1 infection,including natural killer cell mediated cytotoxicity pathway.The circRNAmiRNA-mRNA interaction network included 14 circRNAs,17 miRNAs and 129 mRNAs,another dataset verified the differential expressions of 15 mRNAs downstream,and genes that might be regulated by circRNA mainly included FOXP4,GP6,C9orf116,etc.In the circRNA-miRNA-mRNAinteraction network,circRNA_chr1:39804878|39808198 and circRNA_chr18:44701174|44703102 might influence HIV disease progression by acting as miRNA sponges to regulate the expression of their target genes NUML and Cav-1.Conclusion:Compared with TPs,most of the circRNA expressions in PBMCs of LTNPs are down-regulated,circRNA parental genes are mainly enriched in inflammatory and immune pathways associated with HIV infection,and circRNA can also participate in the regulation of HIV disease progression by acting as a sponge of miRNA,which provides a new direction for studying the mechanism of HIV disease progression.

关 键 词：HIV-1 环状RNA 长期不进展者 表达谱 

分 类 号：R392[医药卫生—免疫学]