Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.jhep.2009.12.043
Title: Lethal-7 is down-regulated by the hepatitis B virus x protein and targets signal transducer and activator of transcription 3
Authors: Wang, Y.
Toh, S.T. 
Lee, C.G.L. 
Lu, Y.
Sung, W.-K. 
Tan, P.
Chow, P.
Chung, A.Y.F.
Jooi, L.L.P.
Keywords: Hepatitis B virus x protein
Hepatocellular carcinoma
let-7
microRNAs
Signal transducer and activator of transcription 3
Issue Date: 2010
Source: Wang, Y.,Toh, S.T.,Lee, C.G.L.,Lu, Y.,Sung, W.-K.,Tan, P.,Chow, P.,Chung, A.Y.F.,Jooi, L.L.P. (2010). Lethal-7 is down-regulated by the hepatitis B virus x protein and targets signal transducer and activator of transcription 3. Journal of Hepatology 53 (1) : 57-66. ScholarBank@NUS Repository. https://doi.org/10.1016/j.jhep.2009.12.043
Abstract: Background & Aims: The pleiotropic hepatitis B virus (HBV) x protein (HBx), associated with hepatocellular carcinoma (HCC), has been implicated in the deregulation of cellular gene expression at the transcriptional level. To date, it remains unknown if HBx regulates the expression of miRNAs which play important roles in gene-regulation at the post-transcriptional and/or translational level. Methods: miRNA microarrays were employed to compare the expression of cellular miRNAs in HBx-versus control-HepG2 cells. Reverse-transcription Taqman realtime-PCR was used to examine let-7a expression in normal liver as well as paired HCC-tumor and adjacent non-tumorous liver. Let-7a miRNA was functionally characterized in cells with transiently altered let-7a expression. The direct target of let-7a was identified in silico and validated using 3′UTR-reporter assay. Results: HBx up-regulates 7 and down-regulates 11 miRNAs, including the let-7 family. HBx expression was found to have a significant inverse correlation with the expression of the highly-expressed members of the let-7 family in HCC patients, highlighting the clinical relevance of our observations. Further characterization of let-7a, the most highly expressed let-7 family member, revealed that it negatively regulates cellular proliferation partly through targeting signal transducer and activator of transcription 3 (STAT3). HBx-mediated down-regulation of let-7a and up-regulation of STAT3 supports cell proliferation in HBx cells. Conclusion: This study thus represents the first demonstration of HBx's ability to deregulate cellular miRNA expression. The deregulation of the expression of the let-7 family of miRNAs by HBx may represent a potential novel pathway through which HBx acts to deregulate cell proliferation leading to hepatocarcinogenesis. © 2010 European Association for the Study of the Liver.
Source Title: Journal of Hepatology
URI: http://scholarbank.nus.edu.sg/handle/10635/28868
ISSN: 01688278
DOI: 10.1016/j.jhep.2009.12.043
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

124
checked on Dec 12, 2017

Page view(s)

214
checked on Dec 15, 2017

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.