Document Detail

Hepatitis B virus X protein represses miRNA-148a to enhance tumorigenesis.
MedLine Citation:
PMID:  23321675     Owner:  NLM     Status:  MEDLINE    
MicroRNAs (miRNAs) have been shown to be dysregulated in virus-related cancers; however, miRNA regulation of virus-related cancer development and progression remains poorly understood. Here, we report that miR-148a is repressed by hepatitis B virus (HBV) X protein (HBx) to promote cancer growth and metastasis in a mouse model of hepatocellular carcinoma (HCC). Hematopoietic pre-B cell leukemia transcription factor-interacting protein (HPIP) is an important regulator of cancer cell growth. We used miRNA target prediction programs to identify miR-148a as a regulator of HPIP. Expression of miR-148a in hepatoma cells reduced HPIP expression, leading to repression of AKT and ERK and subsequent inhibition of mTOR through the AKT/ERK/FOXO4/ATF5 pathway. HBx has been shown to play a critical role in the molecular pathogenesis of HBV-related HCC. We found that HBx suppressed p53-mediated activation of miR-148a. Moreover, expression of miR-148a was downregulated in patients with HBV-related liver cancer and negatively correlated with HPIP, which was upregulated in patients with liver cancer. In cultured cells and a mouse xenograft model, miR-148a reduced the growth, epithelial-to-mesenchymal transition, invasion, and metastasis of HBx-expressing hepatocarcinoma cells through inhibition of HPIP-mediated mTOR signaling. Thus, miR-148a activation or HPIP inhibition may be a useful strategy for cancer treatment.
Xiaojie Xu; Zhongyi Fan; Lei Kang; Juqiang Han; Chengying Jiang; Xiaofei Zheng; Ziman Zhu; Huabo Jiao; Jing Lin; Kai Jiang; Lihua Ding; Hao Zhang; Long Cheng; Hanjiang Fu; Yi Song; Ying Jiang; Jiahong Liu; Rongfu Wang; Nan Du; Qinong Ye
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-16
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  123     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-04-19     Completed Date:  2013-05-13     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  630-45     Citation Subset:  AIM; IM    
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People’s Republic of China.
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MeSH Terms
Base Sequence
Carcinoma, Hepatocellular / etiology*,  genetics,  metabolism,  secondary
Epithelial-Mesenchymal Transition
Hep G2 Cells
Hepatitis B virus / pathogenicity
Liver Neoplasms / etiology*,  genetics,  metabolism
Liver Neoplasms, Experimental / etiology,  genetics,  metabolism
Mice, Nude
MicroRNAs / antagonists & inhibitors,  genetics*
Neoplasm Invasiveness
Signal Transduction
TOR Serine-Threonine Kinases / genetics,  metabolism
Trans-Activators / physiology*
Transcription Factors / genetics,  metabolism
Transplantation, Heterologous
Reg. No./Substance:
0/MIRN148 microRNA, human; 0/MicroRNAs; 0/Mirn148 microRNA, mouse; 0/PBXIP1 protein, human; 0/Trans-Activators; 0/Transcription Factors; 0/hepatitis B virus X protein; EC Serine-Threonine Kinases

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