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

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    Name:
    Role of miR-148a in hepatitis B ...
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    Genre
    Journal Article
    Date
    2012-04-09
    Author
    Yuan, K
    Lian, Z
    Sun, B
    Clayton, MM
    Ng, IOL
    Feitelson, MA
    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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    Permanent link to this record
    http://hdl.handle.net/20.500.12613/5469
    
    Metadata
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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.
    Citation to related work
    Public Library of Science (PLoS)
    Has part
    PLoS ONE
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    ae974a485f413a2113503eed53cd6c53
    http://dx.doi.org/10.34944/dspace/5451
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