基于芯片和公共数据库数据分析微RNA在乙型肝炎病毒感染中的可能机制  

Potential mechanism of microRNA in hepatitis B virus infection by using genechip and public database data

作　　者：林升龙 王香梅 马华晳 张冬青 吴雯军 林佳煌 廖资渊 林明华 郑瑞丹 高海兵 Lin Shenglong;Wang Xiangmei;Ma Huaxi;Zhang Dongqing;Wu Wenjun;Lin Jiahuang;Liao Ziyuan;Lin Minghua;Zheng Ruidan;Gao Haibing(Department of Hepatology,Mengchao Hepatobiliary Hospital of Fujian Medical University,Fuzhou 350025,China;Department of Hepatology,Zhengxing Hosptial,Zhangzhou 363000,Fujian Province,China)

机构地区：[1]福建医科大学孟超肝胆医院肝内科,福州350025 [2]漳州正兴医院肝内科,福建省363000

出　　处：《中华传染病杂志》2020年第11期717-722,共6页Chinese Journal of Infectious Diseases

基　　金：福建省卫生计生中青年骨干人才培养项目(2016-ZQN-77);福建省自然科学基金面上项目(2017J01160);福州市感染性疾病医学中心资助项目(2018080306)。

摘　　要：目的探讨微RNA(microRNA,miRNA)表达在乙型肝炎病毒(hepatitis B virus,HBV)感染中的可能机制。方法采集2017年于福建医科大学孟超肝胆医院就诊的4例慢性乙型肝炎(chronic hepatitis B,CHB)患者和4名健康对照者的外周血标本。通过Affymetrix GeneChip microRNA 4.0芯片检测CHB患者和健康对照者的miRNA表达谱,获得CHB相关差异表达miRNA,并结合生物信息学工具和公共数据库分析其功能。结果共有7个miRNA在CHB患者外周血中差异表达,其中miRNA-122-5p[差异表达倍数(log2 fold change,log2 FC)=7.78,P=0.0073]、let-7c-5p(log2FC=3.52,P=0.0196)、miRNA-6794-5p(log2FC=1.15,P=0.0332)和miRNA-1226-5p(log2FC=0.68,P=0.0343)为高表达,miRNA-619-5p(log2FC=-1.83,P=0.0026)、miRNA-1273g-3p(log2FC=-2.69,P=0.0251)和miRNA-4440(log2FC=-3.99,P=0.0478)为低表达。进一步的分析提示这些差异表达miRNA可能直接作用于HBV基因序列,影响病毒复制。其中miRNA-122-5p、miRNA-6794-5p和miRNA-1226-5p可能通过负向调控其靶基因表达,影响富含纤胶凝蛋白-1颗粒体、富含纤胶凝蛋白-1管腔、伪足体和细胞膜褶皱的构成,共同参与细胞膜的运动及细胞基质附着。结论miRNA可能通过影响细胞膜的分子运动使病毒得以侵入肝细胞内,在HBV感染肝细胞过程中起到重要辅助作用。Objective To investigate the potential mechanism of microRNA(miRNA)in hepatitis B virus(HBV)infection.Methods The peripheral blood samples were collected from four chronic hepatitis B(CHB)patients who visited Mengchao Hepatobiliary Hospital of Fujian Medical University in 2017,and those were also collected from four healthy controls.Affymetrix GeneChip microRNA 4.0 was applied to detect the expressions of miRNA between CHB patients and healthy controls.The CHB relative differential expressions of miRNA were obtained.The functions of CHB relative miRNA were analyzed by the combination of bioinformatics tools and public database data.Results A total of seven miRNA were differentially expressed in the peripheral blood of CHB patients.Among them,miRNA-122-5p(log2 fold change(log2FC)=7.78,P=0.0073),let-7c-5p(log2FC=3.52,P=0.0196),miRNA-6794-5p(log2FC=1.15,P=0.0332),and miRNA-1226-5p(log2FC=0.68,P=0.0343)were up-regulated,while miRNA-619-5p(log2FC=-1.83,P=0.0026),miRNA-1273g-3p(log2FC=-2.69,P=0.0251),and miRNA-4440(log2FC=-3.99,P=0.0478)were down-regulated.Further analysis showed that these miRNA could directly interact with HBV gene sequence and impact the replication of the virus.Among them,miRNA-122-5p,miRNA-6794-5p and miRNA-1226-5p could negatively regulate target genes expression to influence the formation of ficolin-1 rich granule,ficolin-1 rich granule lumen,podosome and membrane ruffle,which participated in the cell membrane movement and cell-matrix adhesion.Conclusion MiRNA could impact the molecular movement in the cell membrane and facilitate HBV entry to liver cells,playing an important supporting role in HBV infection process.

关 键 词：肝炎病毒 乙型 感染 微RNA芯片 公共数据库 细胞膜运动 

分 类 号：R512.62[医药卫生—内科学]