RUNX3 exerts tumor-suppressive role through inhibiting EXOSC4 expression

Related Experiment Video

Updated: Jun 23, 2025

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
09:16

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells

Published on: September 1, 2019

7.5K

Nan Wang1, Xiaodan Miao1, Wenxin Lu1

  • 1Department of Pathology, Xuzhou Medical University, Xuzhou, China.

Functional & Integrative Genomics
|June 24, 2024
PubMed

Insights

RUNX3 suppresses estrogen receptor positive breast cancer by inhibiting EXOSC4 expression. This mechanism impacts cancer stem cell traits and patient survival, highlighting RUNX3

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Estrogen receptor-positive (ER+) breast cancer, prevalent in 70% of cases, is significantly impacted by cancer stem cells (CSCs) driving relapse and metastasis.
  • RUNX3, a tumor suppressor, is frequently inactivated in ER+ breast cancer, but its role in regulating CSC traits remains unclear.
  • Understanding RUNX3's regulatory mechanisms in ER+ breast cancer is crucial for developing targeted therapies.

Purpose of the Study:

  • To elucidate the mechanism by which RUNX3 regulates cancer stem cell traits in estrogen receptor-positive breast cancer.
  • To identify direct targets of RUNX3 involved in breast cancer progression.
  • To investigate the functional role of EXOSC4 in breast cancer stemness and patient survival.

Main Methods:

  • Utilized cut-and-tag assay in BT474 and T47D cells to determine RUNX3 binding profiles.
  • Investigated the effect of EXOSC4 on breast cancer cell proliferation, invasion, and mammosphere formation.
  • Analyzed the correlation between EXOSC4 expression and patient survival in Luminal B/Her2 breast cancer subtypes.

Main Results:

  • Confirmed EXOSC4 as a direct transcriptional target of RUNX3, with RUNX3 binding to the EXOSC4 promoter to suppress its expression.
  • Demonstrated that increased EXOSC4 expression enhances colony formation, invasion, and mammosphere formation, upregulating SOX2 and ALDH1.
  • Found that higher EXOSC4 levels are associated with poorer survival in Luminal B/Her2 breast cancer patients, indicating its role in mediating RUNX3's tumor-suppressive function.

Conclusions:

  • RUNX3 directly suppresses EXOSC4 expression by binding to its promoter region in ER+ breast cancer cells.
  • EXOSC4 promotes breast cancer stemness and is linked to adverse patient outcomes, mediating the tumor-suppressive role of RUNX3.
  • This study reveals a novel RUNX3-EXOSC4 axis critical for understanding and potentially targeting ER+ breast cancer progression.
Keywords:
Breast cancerCancer stem cellsEXOSC4Estrogen receptorRUNX3

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