Genome-wide identification of TCF7L2/TCF4 target miRNAs reveals a role for miR-21 in Wnt-driven epithelial cancer

  • Authors:
    • Fengming Lan
    • Xiao Yue
    • Lei Han
    • Zhendong Shi
    • Yang Yang
    • Peiyu Pu
    • Zhi Yao
    • Chunsheng Kang
  • View Affiliations

  • Published online on: September 28, 2011     https://doi.org/10.3892/ijo.2011.1215
  • Pages:519-526
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Abstract

Transcription factor 7 like 2 (TCF7L2, also known as TCF4) is a Wnt signaling pathway transcription factor involved in regulation of numerous Wnt targeted genes. Recently, thousands of high-confidence TCF4 binding sites were reported in LS174T colon carcinoma cells, however, potential TCF4 target miRNAs remain largely unknown. Here, we utilized a bioinformatics approach to discover 26 miRNA transcription start sites (TSSs) within close proximity to TCF4 chromatin occupancy sites, and validated these sites as bona fide TCF4 targets in LS174T colon carcinoma cells, MCF-7 breast cancer cells and U87 glioma cells by ChIP-PCR. We then selected miR-21 to demonstrate for the first time direct TCF4 transcriptional activation of a miRNA via binding to the promoter region. Tissue array analysis supported this finding, revealing a positive correlation between activation of the β-catenin pathway and in situ expression of miR-21. Finally, based upon the well known but poorly understood preventive effect of aspirin on colorectal cancer incidence and mortality, we report downregulation of miR-21 upon administration of aspirin. In sum, our findings identify direct transcriptional regulation of miR-21 by TCF4 and suggest a role for miR-21 in cancer cell proliferation and invasion upon activation of β-catenin/TCF4 signaling.

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February 2012
Volume 40 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
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Copy and paste a formatted citation
APA
Lan, F., Yue, X., Han, L., Shi, Z., Yang, Y., Pu, P. ... Kang, C. (2012). Genome-wide identification of TCF7L2/TCF4 target miRNAs reveals a role for miR-21 in Wnt-driven epithelial cancer. International Journal of Oncology, 40, 519-526. https://doi.org/10.3892/ijo.2011.1215
MLA
Lan, F., Yue, X., Han, L., Shi, Z., Yang, Y., Pu, P., Yao, Z., Kang, C."Genome-wide identification of TCF7L2/TCF4 target miRNAs reveals a role for miR-21 in Wnt-driven epithelial cancer". International Journal of Oncology 40.2 (2012): 519-526.
Chicago
Lan, F., Yue, X., Han, L., Shi, Z., Yang, Y., Pu, P., Yao, Z., Kang, C."Genome-wide identification of TCF7L2/TCF4 target miRNAs reveals a role for miR-21 in Wnt-driven epithelial cancer". International Journal of Oncology 40, no. 2 (2012): 519-526. https://doi.org/10.3892/ijo.2011.1215