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Gene expression profiles in an hepatitis B virus transfected hepatoblastoma cell line and differentially regulated gene expression by interferon-α

机译:乙肝病毒转染的肝母细胞瘤细胞系中的基因表达谱和干扰素-α差异调控的基因表达

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摘要

AIM: To study interactions between hepatitis B virus (HBV) and interferon-α in liver-derived cells.METHODS: mRNAs were separately isolated from an HBV-transfected cell line (HepG22.2.15) and its parental cell line (HepG2) pre- and post-interferon-α (IFN-α) treatment at 6, 24 and 48 h, followed by hybridization with a cDNA microarray filter dotted with 14 000 human genes. After hybridization and scanning of the arrays, the data were analyzed using ArrayGauge software. The microarray data were further verified by Northern blot analysis.RESULTS: Compared to HepG2 cells, 14 genes with known functions were down-regulated 3 to 12-magnitudes, while 7 genes were up-regulated 3-13 magnitudes in HepG22.2.15 cells prior to IFN-α treatment. After interferon-α treatment, the expression of four genes (vascular endothelial growth factor, tyrosine phosphate 1E, serine protein with IGF-binding motif and one gene of clathrin light chain) in HepG22.2.15 were up-regulated, while one gene encoding a GTP-binding protein, two genes of interferon-induced kinases and two proto-oncogenes were further down-regulated. Interestingly, under IFN-α treatment, a number of differentially regulated genes were new ESTs or genes with unknown functions.CONCLUSION: The up-regulated genes in HepG22.2.15 cell line suggested that under IFN-α treatment, these repressed cellular genes in HBV infected hepatocytes could be partially restored, while the down-regulated genes were most likely the cellular genes which could not be restored under interferon treatment. These down-regulated genes identified by microarray analysis could serve as new targets for anti-HBV drug development or for novel therapies.
机译:目的:研究肝源性细胞中乙型肝炎病毒(HBV)与干扰素-α之间的相互作用。方法:分别从转染HBV的细胞系(HepG22.2.15)和其亲本细胞系(HepG2)中分离mRNA。并在6、24和48小时进行干扰素-α(IFN-α)处理,然后与点缀有14 000个人类基因的cDNA微阵列滤膜杂交。杂交并扫描阵列后,使用ArrayGauge软件分析数据。结果:与HepG2细胞相比,在HepG22.2.15细胞中,与HepG2细胞相比,有14个已知功能基因被下调3至12个大小,而7个基因被上调3-13个大小。进行IFN-α治疗。干扰素-α处理后,HepG22.2.15中的四个基因(血管内皮生长因子,磷酸酪氨酸磷酸化1E,具有IGF结合基序的丝氨酸蛋白和网格蛋白轻链的一个基因)的表达上调,而一个编码α GTP结合蛋白,干扰素诱导的激酶的两个基因和两个原癌基因被进一步下调。有趣的是,在IFN-α处理下,许多差异调节基因是新的EST或功能未知的基因。结论:HepG22.2.15细胞系中的上调基因提示,在IFN-α处理下,这些基因抑制了HBV的细胞基因。被感染的肝细胞可以部分恢复,而下调的基因很可能是在干扰素治疗下无法恢复的细胞基因。通过微阵列分析确定的这些下调基因可以作为抗HBV药物开发或新疗法的新靶标。

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