摘要
Background MicroRNAs （miRNAs） are highly conserved small non-coding RNAs of 18-25 nucleotides （nt） that mediate post-transcriptional gene regulation. Hepatitis B virus （HBV） can cause either acute or chronic hepatitis B, and is a high risk factor for liver cirrhosis and hepatocellular carcinoma. Some mammalian viruses have been shown to modulate the expression of host cellular miRNAs. However, interactions between the HBV and the host cellular miRNAs are largely unknown.Methods miRNA microarray and Northern blotting analysis were used to compare the expression profile of cellular miRNAs of a stable HBV-expressing cell line HepG2.2.15 and its parent cell line HepG2. mRNA microarray assay and the miRanda program were used to predict the miRNA targets. A flow cytometric assay was further used to investigate the expression of human leukocyte antigen （HLA）-A.Results Eighteen miRNAs were differentially expressed between the two cell lines. Among them, eleven were up-regulated and seven were down-regulated in HepG2.2.15 cells. Northern blotting analysis confirmed that the expression of miR-181a, miR-181b, miR-200b and miR-146a were up-regulated and the expression of miR-15a was down-regulated, which was in consistent with the results of the microarray analysis. Furthermore, some putative miRNA targets were predicted and verified to be linked with mRNA expression. The 3′-UTR of HLA-A gene had one partially complementary site for miR-181a and miR-181 a might down-regulate the expression of HLA-A.Conclusion HBV replication modulates the expression of host cellular miRNAs, which may play a role in the pathogenesis of HBV-related liver diseases.
Background MicroRNAs （miRNAs） are highly conserved small non-coding RNAs of 18-25 nucleotides （nt） that mediate post-transcriptional gene regulation. Hepatitis B virus （HBV） can cause either acute or chronic hepatitis B, and is a high risk factor for liver cirrhosis and hepatocellular carcinoma. Some mammalian viruses have been shown to modulate the expression of host cellular miRNAs. However, interactions between the HBV and the host cellular miRNAs are largely unknown.Methods miRNA microarray and Northern blotting analysis were used to compare the expression profile of cellular miRNAs of a stable HBV-expressing cell line HepG2.2.15 and its parent cell line HepG2. mRNA microarray assay and the miRanda program were used to predict the miRNA targets. A flow cytometric assay was further used to investigate the expression of human leukocyte antigen （HLA）-A.Results Eighteen miRNAs were differentially expressed between the two cell lines. Among them, eleven were up-regulated and seven were down-regulated in HepG2.2.15 cells. Northern blotting analysis confirmed that the expression of miR-181a, miR-181b, miR-200b and miR-146a were up-regulated and the expression of miR-15a was down-regulated, which was in consistent with the results of the microarray analysis. Furthermore, some putative miRNA targets were predicted and verified to be linked with mRNA expression. The 3′-UTR of HLA-A gene had one partially complementary site for miR-181a and miR-181 a might down-regulate the expression of HLA-A.Conclusion HBV replication modulates the expression of host cellular miRNAs, which may play a role in the pathogenesis of HBV-related liver diseases.
基金
This study was supported by the grants from the National Natural Science Foundation of China （No. 30700714） and the Major State Basic Research Development Program of China （973 Program, No. 2007CB512803）.Acknowledgement： We thank Dr. ZHANG Liang from Beijing Capital Bio Corporation of China for his helpful advice and comments.
