MicroRNAs-372/373 promote the expression of hepatitis B Virus through the targeting of nuclear factor I/B.

[Guest guest]

Hepatology. 2011 May 23. doi: 10.1002/hep.24441. [Epub ahead of print]

MicroRNAs-372/373 promote the expression of hepatitis B Virus through the

targeting of nuclear factor I/B.

Guo H, Liu H, Mitchelson K, Rao H, Luo M, Xie L, Sun Y, Zhang L, Lu Y, Liu R,

Ren A, Liu S, Zhou S, Zhu J, Zhou Y, Huang A, Wei L, Guo Y, Cheng J.

Source

Medical Systems Biology Research Center, Department of Biomedical Engineering,

Tsinghua University School of Medicine, Beijing, China; National Engineering

Research Center for Beijing Biochip Technology, Beijing, China.

Abstract

MicroRNAs (miRNAs) play important roles in the posttranscriptional regulation of

gene expression. Recent evidence has indicated the pathological relevance of

miRNA dyregulation in hepatitis virus infection, however the roles of microRNAs

in the regulation of hepatitis B virus (HBV) expression are still largely

unknown. In this study, we have identified that miR-373 was upregulated in

HBV-infected liver tissues and that the members of the miRs-371-372-373

(miRs-371-3) gene cluster were also significantly co-upregulated in

HBV-producing HepG2.2.15 cells. A positive in vivo association was identified

between hepatic HBV DNA levels and the copy number variation of the miRs-371-3

gene cluster. The enhanced expression of miRs-372/373 stimulated the production

of HBV proteins and HBV core-associated DNA in HepG2 cells transfected with

1.3×HBV. Further, nuclear factor I/B (NFIB) was identified to be a direct

functional target of miRs-372/373 by in silico algorithms and this was

subsequently was confirmed by western blotting and luciferase reporter assays.

Knockdown of NFIB by siRNA promoted HBV expression, whereas rescue of NFIB

attenuated the stimulation in the 1.3×HBV transfected HepG2 cells. Conclusion:

Our study revealed that the miRNA (miRs-372/373) can promote HBV expression

through a pathway involving the transcription factor (NFIB). This novel model

provides new insights into the molecular basis in HBV and host interaction.

(HEPATOLOGY 2011.).

Copyright © 2011 American Association for the Study of Liver Diseases.

PMID: 21608007 [PubMed - as supplied by publisher]

[Guest guest]

Hepatology. 2011 May 23. doi: 10.1002/hep.24441. [Epub ahead of print]

MicroRNAs-372/373 promote the expression of hepatitis B Virus through the

targeting of nuclear factor I/B.

Guo H, Liu H, Mitchelson K, Rao H, Luo M, Xie L, Sun Y, Zhang L, Lu Y, Liu R,

Ren A, Liu S, Zhou S, Zhu J, Zhou Y, Huang A, Wei L, Guo Y, Cheng J.

Source

Medical Systems Biology Research Center, Department of Biomedical Engineering,

Tsinghua University School of Medicine, Beijing, China; National Engineering

Research Center for Beijing Biochip Technology, Beijing, China.

Abstract

MicroRNAs (miRNAs) play important roles in the posttranscriptional regulation of

gene expression. Recent evidence has indicated the pathological relevance of

miRNA dyregulation in hepatitis virus infection, however the roles of microRNAs

in the regulation of hepatitis B virus (HBV) expression are still largely

unknown. In this study, we have identified that miR-373 was upregulated in

HBV-infected liver tissues and that the members of the miRs-371-372-373

(miRs-371-3) gene cluster were also significantly co-upregulated in

HBV-producing HepG2.2.15 cells. A positive in vivo association was identified

between hepatic HBV DNA levels and the copy number variation of the miRs-371-3

gene cluster. The enhanced expression of miRs-372/373 stimulated the production

of HBV proteins and HBV core-associated DNA in HepG2 cells transfected with

1.3×HBV. Further, nuclear factor I/B (NFIB) was identified to be a direct

functional target of miRs-372/373 by in silico algorithms and this was

subsequently was confirmed by western blotting and luciferase reporter assays.

Knockdown of NFIB by siRNA promoted HBV expression, whereas rescue of NFIB

attenuated the stimulation in the 1.3×HBV transfected HepG2 cells. Conclusion:

Our study revealed that the miRNA (miRs-372/373) can promote HBV expression

through a pathway involving the transcription factor (NFIB). This novel model

provides new insights into the molecular basis in HBV and host interaction.

(HEPATOLOGY 2011.).

Copyright © 2011 American Association for the Study of Liver Diseases.

PMID: 21608007 [PubMed - as supplied by publisher]