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Updated: May 30, 2026

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
Published on: September 1, 2019
Absence of Runx3 expression in normal gastrointestinal epithelium calls into question its tumour suppressor function
Ditsa Levanon1, Yael Bernstein, Varda Negreanu
1Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
Abstract:
The Runx3 transcription factor regulates cell fate decisions during embryonic development and in adults. It was previously reported that Runx3 is strongly expressed in embryonic and adult gastrointestinal tract (GIT) epithelium (Ep) and that its loss causes gastric cancer. More than 280 publications have based their research on these findings and concluded that Runx3 is indeed a tumour suppressor (TS). In stark contrast, using various measures, we found that Runx3 expression is undetectable in GIT Ep. Employing a variety of biochemical and genetic techniques, including analysis of Runx3-GFP and R26LacZ/Runx3(Cre) or R26tdTomato/Runx3(Cre) reporter strains, we readily detected Runx3 in GIT-embedded leukocytes, dorsal root ganglia, skeletal elements and hair follicles. However, none of these approaches revealed detectable Runx3 levels in GIT Ep. Moreover, our analysis of the original Runx3(LacZ/LacZ) mice used in the previously reported study failed to reproduce the GIT expression of Runx3. The lack of evidence for Runx3 expression in normal GIT Ep creates a serious challenge to the published data and undermines the notion that Runx3 is a TS involved in cancer pathogenesis.
Insights
This study challenges the established role of Runx3 as a tumor suppressor in the gastrointestinal tract (GIT). Researchers found no detectable Runx3 expression in GIT epithelium, contradicting previous findings and impacting cancer research.
Area of Science:
- Developmental Biology
- Cancer Biology
- Molecular Genetics
Background:
- The transcription factor Runx3 is widely considered a tumor suppressor (TS) in the gastrointestinal tract (GIT).
- Previous studies reported strong Runx3 expression in GIT epithelium (Ep), linking its loss to gastric cancer.
- Over 280 publications have relied on these findings to establish Runx3's TS role.
Purpose of the Study:
- To investigate the actual expression pattern of Runx3 in the gastrointestinal tract.
- To re-evaluate the role of Runx3 as a tumor suppressor in GIT cancer pathogenesis.
Main Methods:
- Utilized various biochemical and genetic techniques.
- Analyzed Runx3-GFP, R26LacZ/Runx3(Cre), and R26tdTomato/Runx3(Cre) reporter mouse strains.
- Examined original Runx3(LacZ/LacZ) mice from prior studies.
Main Results:
- Runx3 expression was undetectable in GIT epithelium across all tested methods.
- Runx3 was detected in GIT-embedded leukocytes, dorsal root ganglia, skeletal elements, and hair follicles.
- Previous findings of Runx3 expression in GIT Ep could not be reproduced.
Conclusions:
- The absence of Runx3 expression in normal GIT epithelium challenges established data.
- The notion of Runx3 as a tumor suppressor in GIT cancer is undermined by these findings.
- Further research is needed to clarify Runx3's function and its role in cancer.
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