TIPUH1 encodes a novel KRAB zinc-finger protein highly expressed in human hepatocellular carcinomas

Abstract

To achieve a better understanding of mechanisms that underlie hepatocarcinogenesis and to identify novel target molecules for diagnosis and therapy of hepatocellular carcinoma (HCC), we previously analysed gene-expression profiles of 20 HCC tissues on a cDNA microarray. Among the genes upregulated in the tumor tissues compared with their nontumor counterparts, we focused on a novel gene termed transcription-involved protein upregulated in HCC (TIPUH1) that putatively encoded a 500-amino-acid protein containing 12 zinc-finger domains and a Kruppel-associated box domain. Multiple-tissue northern blot analysis revealed it's testis- and placenta-specific expression in normal tissues. Colony-formation assay in soft agar showed that TIPUH1 conferred anchorage-independent growth to NIH3T3 cells, suggesting its oncogenic activity. Conversely, specific siRNA for TIPUH1 knocked down its expression in HCC cells, which resulted in their growth inhibition. We identified four TIPUH1-interacting proteins including TIF1beta, a transcription-intermediary protein, and three involved in pre-mRNA processing (hnRNPU, hnRNPF, and Nucleolin), suggesting that overexpressed TIPUH1 may play a role in hepatocarcinogenesis by regulating transcription and/or RNA processing of growth control genes. These data may contribute to a better understanding of liver neoplasia, and to the development of novel strategy for treatment of HCCs.