Novel candidate targets of Wnt/β-catenin signaling in hepatoma cells

Heun Sik Lee, Mee Hee Park, Suk Jin Yang, Kyung Chan Park, Nam Soon Kim, Yong Sung Kim, Dae Il Kim, Hyang Sook Yoo, Eui Ju Choi, Young Il Yeom

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The activity of β-catenin/TCF, the key component of Wnt signaling pathway, is frequently deregulated in HCC, resulting in the activation of genes whose dysregulation has significant consequences on tumor development. Therefore, identifying the target genes of Wnt signaling is important for understanding β-catenin-mediated carcinogenesis. We analyzed the transcriptome profile of human hepatoma cell lines using cDNA microarrays representing 15,127 unique, liver-enriched gene loci to identify the target genes of β-catenin-mediated transcription (p < 0.005). This analysis yielded 130 potential Wnt-associated classifier genes, and we found 33 of them contain consensus TCF-binding sites in presumptive transcriptional regulatory sequences. These genes were, then, tested for their Wnt-dependence of expression in experimental models of Wnt activation. Genes such as RPL29, NEDD4L, FUT8, LYZ, STMN2, STARD7 and KIAA0998 were proven to be up-regulated upon Wnt/β-catenin activation. Gene ontology analysis of the 33 candidate genes indicated the presence of functional categories relevant to Wnt pathway such as cell growth, proliferation, adhesion and signal transduction. In conclusion, we identified a number of candidate Wnt/β-catenin target genes that can be useful for studying the role of altered Wnt signaling in liver cancer development, and showed that some of them might be direct targets of Wnt signaling in hepatoma cells.

Original languageEnglish
Pages (from-to)690-698
Number of pages9
JournalLife Sciences
Volume80
Issue number7
DOIs
Publication statusPublished - 2007 Jan 23

Keywords

  • HCC
  • Target genes
  • Wnt/β-catenin
  • cDNA microarray

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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  • Cite this

    Lee, H. S., Park, M. H., Yang, S. J., Park, K. C., Kim, N. S., Kim, Y. S., Kim, D. I., Yoo, H. S., Choi, E. J., & Yeom, Y. I. (2007). Novel candidate targets of Wnt/β-catenin signaling in hepatoma cells. Life Sciences, 80(7), 690-698. https://doi.org/10.1016/j.lfs.2006.10.024