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Role of mir-148a in hepatitis B associated hepatocellular carcinoma

Yuan, K
; 
Lian, Z
; 
Sun, B
; 
Clayton, MM
; 
Ng, IOL
; 
Feitelson, MA
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Genre
Journal Article
Date
2012-04-09
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Department
Subject
3' Untranslated Regions
 Adult
 Aged
 Animals
 Carcinoma, Hepatocellular
 Cell Cycle
 Cell Line, Tumor
 Cell Movement
 Cell Proliferation
 Female
 Hepatitis B
 Humans
 Liver Neoplasms
 Male
 Mice
 Mice, SCID
 MicroRNAs
 Middle Aged
 PTEN Phosphohydrolase
 Proto-Oncogene Proteins c-akt
 Trans-Activators
 Viral Regulatory and Accessory Proteins
 beta Catenin
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http://hdl.handle.net/20.500.12613/5469
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Role of miR-148a in hepatitis B associated hepatocellular carcinoma.pdf
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DOI
10.1371/journal.pone.0035331
Abstract
Hepatitis B virus encoded X antigen (HBx) is a trans-regulatory protein that alters the activity of selected transcription factors and cytoplasmic signal transduction pathways. HBx transcriptionally up-regulates the expression of a unique gene, URG11, which in turn transcriptionally up-regulates β-catenin, thereby contributing importantly to hepatocarcinogenesis. HBx and URG11 also alter the expression of multiple microRNAs, and by miRNA array analysis, both were shown to promote the expression of miR-148a. Elevated miR-148a was also seen in HBx positive liver samples from infected patients. To study the function of miR-148a, anti-148a was introduced into HepG2 and Hep3B cells stably expressing HBx or stably over-expressing URG11. Anti-miR-148a suppressed cell proliferation, cell cycle progression, cell migration, anchorage independent growth in soft agar and subcutaneous tumor formation in SCID mice. Introduction of anti-miR-148a increased PTEN protein and mRNA expression, suggesting that PTEN was targeted by miR-148a. Anti-miR-148a failed to suppress PTEN expression when co-transfected with reporter gene mutants in the 3′UTR of PTEN mRNA. Introduction of anti-miR-148a also resulted in depressed Akt signaling by HBx and URG11, resulting in decreased expression of β-catenin. Thus, miR-148a may play a central role in HBx/URG11 mediated HCC, and may be an early diagnostic marker and/or therapeutic target associated with this tumor type. © 2012 Yuan et al.
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