LncRNA expression profiles in HBV‐transformed human hepatocellular carcinoma cells treated with a novel inhibitor of human La protein
LncRNA expression profiles in HBV‐transformed human hepatocellular carcinoma cells treated with a novel inhibitor of human La protein
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DOI：
10.1111/jvh.12821
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发表时间：
2018-04
影响因子：
2.5
通讯作者：
Jiaqian Pan;Jiaqian Pan;Shuangmei Tong;Jing Tang;Jing Tang
中科院分区：
文献类型：
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作者：
Jiaqian Pan;Jiaqian Pan;Shuangmei Tong;Jing Tang;Jing Tang
我们之前发现了一种新的La蛋白抑制剂H11，它通过抑制La蛋白和HBV RNA之间的相互作用来抑制乙型肝炎病毒（HBV）的复制。然而，参与这一过程的其他细胞因素仍不清楚。为了研究H11介导的抑制HBV感染的机制，我们对H11处理和未处理的稳定表达HBV的人肝母细胞瘤HepG2.2.15细胞进行了lncRNA芯片分析。使用基因本体（Gene Ontology， GO）和通路分析生成和分析差异表达的lncrna和mrna的谱。微阵列数据显示，与对照组相比，H11处理组有61个lncrna表达上调，74个lncrna表达下调，43个mrna表达上调，44个mrna表达下调，这些结果与qRT‐PCR表达数据一致。生物信息学分析表明，差异表达的lncrna参与RNA介导的转录后基因沉默、病毒基因组复制调控、Jak - STAT信号通路和细胞凋亡途径。GO分析显示，差异表达的mrna富集于Wnt信号通路的负调控和生长的负调控。通路分析表明，差异表达的mrna参与核β -连环蛋白信号传导和靶基因转录的调节，作为p53的直接效应物，参与过氧化物酶体增殖物激活受体信号传导和过氧化物酶体途径。微阵列数据和qRT‐PCR结果表明，H11通过调节Wnt、β - catenin和PPAR信号通路介导HBV复制抑制。
We previously identified a novel inhibitor of La protein, H11, which inhibited hepatitis B virus (HBV) replication by inhibiting the interaction between La protein and HBV RNA. However, the other cellular factors involved in this process remain unclear. To investigate the mechanism of H11‐mediated inhibition of HBV infection, a lncRNA microarray analysis was performed using H11‐treated and untreated stable HBV‐expressing human hepatoblastoma HepG2.2.15 cells. The profiles of differentially expressed lncRNAs and mRNAs were generated and analysed using Gene Ontology (GO) and pathway analyses. The microarray data showed that 61 lncRNAs were upregulated, 74 lncRNAs were downregulated, 43 mRNAs were upregulated, and 44 mRNAs were downregulated in H11 treatment group when compared with the control group, and these results were consistent with qRT‐PCR expression data. Bioinformatic analysis indicated that the differentially expressed lncRNAs were involved in RNA‐mediated post‐transcriptional gene silencing, regulation of viral genome replication and Jak‐STAT signalling and apoptosis pathways. GO analysis showed that differentially expressed mRNAs were enriched in negative regulation of the Wnt signalling pathway and negative regulation of growth. Pathways analysis indicated that the differentially expressed mRNAs were involved in regulation of nuclear β‐catenin signalling and target gene transcription, as direct p53 effectors, and in the peroxisome proliferator‐activated receptors signalling and peroxisome pathways. Microarray data and qRT‐PCR results indicated that H11 mediates inhibition of HBV replication by regulating the Wnt, β‐catenin and PPAR signalling pathways.