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Updated: May 31, 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
Identification of RUNX3 as a component of the MST/Hpo signaling pathway
Boram Min1, Min-Kyu Kim, Joo-Won Zhang
1Department of Biochemistry, School of Medicine, Chungbuk National University, Cheongju, South Korea.
Abstract:
Recent genetic screens of fly mutants and molecular analysis have revealed that the Hippo (Hpo) pathway controls both cell proliferation and cell death. Deregulation of its human counterpart (the MST pathway) has been implicated in human cancers. However, how this pathway is linked with the known tumor suppressor network remains to be established. RUNX3 functions as a tumor suppressor of gastric cancer, lung cancer, bladder cancer, and colon cancer. Here, we show that RUNX3 is a principal and evolutionarily conserved component of the MST pathway. SAV1/WW45 facilitates the close association between MST2 and RUNX3. MST2, in turn, stimulates the SAV1-RUNX3 interaction. In addition, we show that siRNA-mediated RUNX3 knockdown abolishes MST/Hpo-mediated cell death. By establishing that RUNX3 is an endpoint effector of the MST pathway and that RUNX3 is capable of inducing cell death in cooperation with MST and SAV1, we define an evolutionarily conserved novel regulatory mechanism loop for tumor suppression in human cancers.
Insights
The Hippo-MST pathway regulates cell death and proliferation. This study reveals RUNX3 as a key tumor suppressor in this pathway, crucial for its cancer-fighting function.
Area of Science:
- Molecular Biology
- Cancer Genetics
- Cell Biology
Background:
- The Hippo (Hpo) pathway regulates cell proliferation and death in flies.
- Its human homolog, the MST pathway, is linked to cancer development.
- The connection between the MST pathway and tumor suppressor networks is not well understood.
Purpose of the Study:
- To investigate the role of RUNX3 in the MST pathway.
- To elucidate the molecular mechanisms linking RUNX3 to MST-mediated tumor suppression.
Main Methods:
- Genetic screens in fly mutants
- Molecular analysis
- siRNA-mediated knockdown
Main Results:
- RUNX3 is identified as a conserved component of the MST pathway.
- SAV1/WW45 mediates the interaction between MST2 and RUNX3.
- RUNX3 knockdown inhibits MST/Hpo-induced cell death.
- RUNX3 cooperates with MST and SAV1 to induce cell death.
Conclusions:
- RUNX3 is an endpoint effector of the MST pathway.
- A novel, evolutionarily conserved regulatory loop involving RUNX3, MST, and SAV1 contributes to tumor suppression.
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