The non-coding variant rs1800734 enhances DCLK3 expression through long-range interaction and promotes colorectal cancer progression

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

22 Scopus Citations
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Author(s)

  • Ning Qing Liu
  • Menno Ter Huurne
  • Luan N. Nguyen
  • Tianran Peng
  • Shuang-Yin Wang
  • James B. Studd
  • Onkar Joshi
  • Halit Ongen
  • Jesper B Bramsen
  • Claus L. Andersen
  • Jussi Taipale
  • Emmanouil T. Dermitzakis
  • Richard S. Houlston
  • Nina C. Hubner
  • Hendrik G. Stunnenberg

Detail(s)

Original languageEnglish
Article number14418
Journal / PublicationNature Communications
Volume8
Online published14 Feb 2017
Publication statusOnline published - 14 Feb 2017
Externally publishedYes

Link(s)

Abstract

Genome-wide association studies have identified a great number of non-coding risk variants for colorectal cancer (CRC). To date, the majority of these variants have not been functionally studied. Identification of allele-specific transcription factor (TF) binding is of great importance to understand regulatory consequences of such variants. A recently developed proteome-wide analysis of disease-associated SNPs (PWAS) enables identification of TF-DNA interactions in an unbiased manner. Here we perform a large-scale PWAS study to comprehensively characterize TF-binding landscape that is associated with CRC, which identifies 731 allele-specific TF binding at 116 CRC risk loci. This screen identifies the A-allele of rs1800734 within the promoter region of MLH1 as perturbing the binding of TFAP4 and consequently increasing DCLK3 expression through a long-range interaction, which promotes cancer malignancy through enhancing expression of the genes related to epithelial-to-mesenchymal transition.

Research Area(s)

Citation Format(s)

The non-coding variant rs1800734 enhances DCLK3 expression through long-range interaction and promotes colorectal cancer progression. / Liu, Ning Qing; Ter Huurne, Menno; Nguyen, Luan N.; Peng, Tianran; Wang, Shuang-Yin; Studd, James B.; Joshi, Onkar; Ongen, Halit; Bramsen, Jesper B; Yan, Jian; Andersen, Claus L.; Taipale, Jussi; Dermitzakis, Emmanouil T.; Houlston, Richard S.; Hubner, Nina C.; Stunnenberg, Hendrik G.

In: Nature Communications, Vol. 8, 14418, 14.02.2017.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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