Abstract
SIAH-1 (seven in absentia homologue-1) is an E3-ubiquitin ligase that facilitates labelling and subsequent proteasomal degradation of different proteins like transcription factors (e.g. c-myb) and coactivators (e.g. beta-catenin). Here we show that SIAH-1 expression is frequently reduced in human hepatocarcinogenesis. However, further reduction of SIAH-1 bioavailability by gene-specific siRNA (RNAinterference) in HCC cell lines resulted in significantly decreased tumor cell viability. Therefore we conclude that distinct SIAH-1 levels mediate pro-tumorigenic effects in HCC cells and that further SIAH-1 inhibition may represent a new therapeutic strategy in the treatment of human hepatocellular carcinoma.
MeSH terms
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Antineoplastic Agents / therapeutic use
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Carcinoma, Hepatocellular / enzymology
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Carcinoma, Hepatocellular / genetics*
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Drug Design
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Enzyme Inhibitors / therapeutic use
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Gene Expression Regulation, Neoplastic*
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Humans
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Liver / enzymology
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Liver Neoplasms / enzymology
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Liver Neoplasms / genetics*
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism
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Protein Binding
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RNA, Small Interfering / genetics*
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Reference Values
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Transcription, Genetic
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Ubiquitin-Protein Ligases / antagonists & inhibitors
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Ubiquitin-Protein Ligases / genetics*
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Ubiquitin-Protein Ligases / metabolism
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Nuclear Proteins
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RNA, Small Interfering
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Ubiquitin-Protein Ligases
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seven in absentia proteins