Yin Yang-1Suppresses Differentiation Of Hepatocellular Carcinoma Cells Through The Downregulation Of CCAAT/Enhancer-binding Protein Alpha

As a member of the GLI-Kruppel family of transcriptional factors, Yin Yang-1(YYl) functions as an oncogene in various types of cancers. However, the role of YY1in hepatocelluar carcinogenesis remains unknown. In this report, we investigated the relevance of YY1to hepatocellular carcinoma (HCC) development. We found that YYl was up-regulated in primary liver tumor tissues and HCC cell lines. Ectopic YY1expression promoted the growth of non-tumor liver cells that expressed low level of YY1. In contrast, YYl depletion inhibited the growth of HCC cells which was accompanied with distinct morphological changes. Moreover, the phenotypic changes induced by YYl depletion were attributed to cellular differentiation rather than cellular senescence. CEBPA which was important to regulate differentiation of hepatocytes was found as the direct target downregulated by YY1. Restoration of CEBPA in YYl-expressing HCC cells induced cellular differentiation and growth inhibition while knockdown of CEBPA expression in non-tumor liver cells promoted cell growth. In summary, our study demonstrated that YY1could promote hepatocelluar carcinogenesis and inhibit cellular differentiation through the downregulation of CEBPA expression.