[Reduced expression of the E3-ubiquitin ligase seven in absentia homologue (SIAH)-1 in human hepatocellular carcinoma].

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.