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JUNB mediates oxaliplatin resistance via the MAPK signaling pathway in gastric cancer by chromatin accessibility and

Suyao Li1, Yichou Wei1, Xun Sun1

  • 1Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Acta Biochimica Et Biophysica Sinica
|June 20, 2023
PubMed

Insights

JUNB overexpression drives oxaliplatin resistance in gastric cancer by activating the MAPK pathway. Inhibiting JUNB or using MAPK inhibitors with oxaliplatin can restore sensitivity and improve patient prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Platinum-based chemotherapy, including oxaliplatin, is standard for advanced gastric cancer.
  • Chemotherapy resistance significantly limits treatment efficacy and patient survival.
  • Understanding resistance mechanisms is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying oxaliplatin resistance in gastric cancer.
  • To identify key molecular targets for overcoming oxaliplatin resistance.

Main Methods:

  • Generation of an oxaliplatin-resistant gastric cancer cell line.
  • Assay for transposase-accessible chromatin sequencing (ATAC-seq) and RNA sequencing (RNA-seq).
  • Chromatin immunoprecipitation sequencing (ChIP-seq) and tissue microarray analysis.

Main Results:

  • Identified 3232 genomic regions with higher accessibility in resistant cells, implicating JUNB as a core transcription factor.
  • JUNB overexpression in resistant cells correlates with poor gastric cancer prognosis.
  • JUNB activates the MAPK signaling pathway, mediating oxaliplatin resistance.

Conclusions:

  • JUNB plays a critical role in mediating oxaliplatin resistance in gastric cancer via MAPK pathway activation.
  • Targeting JUNB or combining MAPK inhibitors with oxaliplatin offers a promising strategy to overcome resistance and improve patient outcomes.
Keywords:
ATAC-seqJUNBMAPK signaling pathwaychromatin accessibilitygastric canceroxaliplatin resistance

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