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An antisense transcript induced by Wnt/beta-catenin signaling decreases E2F4

Gregory S Yochum1, Ryan Cleland, Shannon McWeeney

  • 1Vollum Institute, Division of Biostatistics, Department of Public Health and Preventative Medicine, OHSU Cancer Institute, Oregon Health and Science University, Portland 97239, USA. yochumg@ohsu.edu

The Journal of Biological Chemistry
|November 24, 2006
PubMed

Insights

Wnt signaling activates beta-catenin, which can regulate noncoding RNAs. This study found a beta-catenin-induced antisense RNA targeting E2F4 mRNA, potentially contributing to colorectal cancer by reducing E2F4 protein levels.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Biology

Background:

  • Wnt/beta-catenin signaling is crucial in development and cancer, typically regulating protein-coding genes.
  • Genome-wide studies reveal many noncoding transcripts, whose regulation by transcription factors is less understood.
  • Serial analysis of chromatin occupancy (SACO) identifies transcription factor-binding sites for noncoding RNAs.

Purpose of the Study:

  • To identify novel beta-catenin-regulated noncoding transcripts using SACO.
  • To investigate the role of a newly identified antisense RNA in colorectal carcinoma cells.
  • To elucidate the mechanism by which Wnt signaling affects E2F4 expression.

Main Methods:

  • Utilized serial analysis of chromatin occupancy (SACO) to map beta-catenin-binding sites.
  • Identified and characterized a beta-catenin-regulated antisense RNA targeting the E2F4 gene's 3'-untranslated region (3'-UTR).
  • Assessed the impact of the antisense RNA on E2F4 protein levels and its downstream targets using molecular biology techniques.

Main Results:

  • Identified a beta-catenin- and TCF4-bound site in the E2F4 3'-UTR, inducing an antisense RNA.
  • Wnt signaling activation (mimicked by LiCl) increased E2F4 antisense RNA and decreased E2F4 protein levels.
  • The decrease in E2F4 protein was linked to reduced binding of E2F4 to its target genes involved in cell cycle regulation.

Conclusions:

  • Wnt/beta-catenin signaling can regulate gene expression through antisense RNAs.
  • An E2F4 antisense transcript induced by Wnt signaling may suppress E2F4 protein, potentially promoting colorectal carcinogenesis.
  • This finding reveals a novel regulatory mechanism in Wnt signaling and colorectal cancer.

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