Transcription Factor MYB Upregulates IQGAP3 to Mediate DNA Repair and Promote 5-FU Resistance in Gastric Cancer Cells

Strategic Insights -

A groundbreaking study published in the journal Drug Development Research has uncovered the crucial role of the MYB/IQGAP3 axis in mediating 5-Fluorouracil (5-FU) resistance in gastric cancer (GC) cells. The research, led by Piyao Gao and colleagues from Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine, reveals that MYB upregulates IQGAP3 to facilitate DNA repair and promote 5-FU resistance in GC cells.

Key Takeaways:

  • The study found that 5-FU-based chemotherapy is a first-line treatment for advanced GC, but the development of resistance remains a significant limitation to its clinical efficacy.
  • The MYB/IQGAP3 axis plays a crucial role in mediating 5-FU resistance in GC cells, with IQGAP3 involved in regulating mismatch repair and DNA repair pathways.
  • Suppression of IQGAP3 led to increased sensitivity to 5-FU, as evidenced by a decreased IC50 value, increased apoptosis, and restrained proliferation of GC cells.
  • The authors identified a pronounced enhancement in the expression of IQGAP3 and MYB within GC tissues and cells, and detected a regulatory link between MYB and IQGAP3.
  • The study suggested that targeting MYB/IQGAP3 could reduce GC drug resistance and enhance the clinical efficacy of treatments.

Statistics:

  • 5-FU-based chemotherapy is a first-line treatment for advanced GC, but the development of resistance remains a major limitation to its clinical efficacy.
  • The study found that IQGAP3 expression was upregulated in GC tissues and cells, with a significant enhancement observed in the expression of MYB within GC tissues and cells.
  • The IC50 value was decreased by 30.4% in the IQGAP3-suppressed group compared to the control group.
  • Apoptosis was increased by 25.6% in the IQGAP3-suppressed group compared to the control group.
  • The expression of P-gp, MRP1, and GST-p protein levels were downregulated by 23.4%, 24.5%, and 21.7%, respectively, in the IQGAP3-suppressed group.

Sources:

  • Piyao Gao et al. (2025) Transcription Factor MYB Upregulates IQGAP3 to Mediate DNA Repair and Promote 5-FU Resistance in Gastric Cancer Cells. Drug Development Research, 86(5).
  • Drug Development Research. (2025) Wiley, 111 River St, Hoboken 07030-5774, NJ, USA.
  • Gao, P., Huang, L., Xiao, P., Chen, Z., & Zhang, S. (2025). Transcription Factor MYB Upregulates IQGAP3 to Mediate DNA Repair and Promote 5-FU Resistance in Gastric Cancer Cells. Drug Development Research, 86(5), 1-11.