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学科主题: 药学
题名:
Genomic analysis of anti-Hepatitis B virus (HBV) activity by small interfering RNA and lamivudine in stable HBV-producing cells
作者: Guo, Y; Guo, HY; Zhang, L; Xie, HY; Zhao, X; Wang, FX; Li, Z; Wang, YH; Ma, SL; Tao, JP; Wang, WX; Zhou, YX; Yang, WP; Cheng, J
刊名: JOURNAL OF VIROLOGY
发表日期: 2005-11-01
DOI: 10.1128/JVI.79.22.14392-14403.2005
卷: 79, 期:22, 页:14392-14403
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Virology
研究领域[WOS]: Virology
关键词[WOS]: MAMMALIAN-CELLS ; GENE-EXPRESSION ; NUCLEOSIDE ANALOGS ; TRANSGENIC MICE ; MICROARRAY DATA ; CULTURE ASSAY ; IN-VIVO ; REPLICATION ; INHIBITION ; SIRNAS
英文摘要:

Hepatitis B virus (HBV) causes acute and chronic hepatitis and hepatocellular carcinoma. Small interfering RNA (siRNA) and lamivudine have been shown to have anti-HBV effects through different mechanisms. However, assessment of the genome-wide effects of siRNA and lamivudine on HBV-producing cell lines has not been reported, which may provide a clue to interrogate the HBV-cell interaction and to evaluate the siRNA′s side effect as a potential drug. In the present study, we designed seven siRNAs based on the conserved HBV sequences and tested their effects on the expression of HBV genes following sorting of siRNA-positive cells. Among these seven siRNAs, siRNA-1 and siRNA-7 were found to effectively suppress HBV gene expression. We further addressed the global gene expression changes in stable HBV-producing cells induced by siRNA-1 and siRNA-7 by use of human genome-wide oligonucleotide microarrays. Data from the gene expression profiling indicated that siRNA-1 and siRNA-7 altered the expression of 54 and 499 genes, respectively, in HepG2.2.15 cells, which revealed that different siRNAs had various patterns of gene expression profiles and suggested a complicated influence of siRNAs on host cells. We further observed that 18 of these genes were suppressed by both siRNA-1 and siRNA-7. Interestingly, seven of these genes were originally activated by HBV, which suggested that these seven genes might be involved in the HBV-host cell interaction. Finally, we have compared the effects of siRNA and lamivudine on HBV and host cells, which revealed that siRNA is more effective at inhibiting HBV expression at the mRNA and protein level in vitro, and the gene expression profile of HepG2.2.15 cells treated by lamivudine is totally different from that seen with siRNA.

语种: 英语
WOS记录号: WOS:000232997500055
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67181
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Tsing Hua Univ, Sch Med, Med Syst Biol Res Ctr, Beijing 100084, Peoples R China
2.Tsing Hua Univ, Dept Biol Sci & Biotechnol, Beijing 100084, Peoples R China
3.Tsing Hua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China
4.Natl Engn Res Ctr Beijing Biochip Technol, Beijing 102206, Chagping Dist, Peoples R China
5.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100083, Peoples R China
6.CapitalBio Corp, Beijing 102206, Changping Dist, Peoples R China

Recommended Citation:
Guo, Y,Guo, HY,Zhang, L,et al. Genomic analysis of anti-Hepatitis B virus (HBV) activity by small interfering RNA and lamivudine in stable HBV-producing cells[J]. JOURNAL OF VIROLOGY,2005,79(22):14392-14403.
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