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DOT1L promotes expression of CD44 through the Wnt/β-catenin signaling pathway in early gastric carcinoma

  • 0Department of Pathology, Jiangnan University Medical Center, Wuxi, Jiangsu Province 214002, PR China.
Journal of Cancer +

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March 18, 2024

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March 18, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Telomere silencing 1-like (DOT1L) gene is upregulated in gastric cancer (GC) and promotes cancer stem cell (CSC) development by increasing CD44 expression via the Wnt/β-catenin pathway. DOT1L is a potential regulator of stemness in GC.

Area Of Science

  • Oncology
  • Molecular Biology
  • Genetics

Background

  • Gastric cancer (GC) progression involves epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) activation.
  • The role of telomere silencing 1-like (DOT1L) in GC stemness and EMT remains to be fully elucidated.

Purpose Of The Study

  • To investigate DOT1L gene expression in gastric cancer tissues.
  • To determine the function of DOT1L in promoting CSC-mediated EMT in GC.
  • To explore the underlying molecular mechanisms of DOT1L in GC stemness.

Main Methods

  • Whole-exome sequencing and single-cell transcriptomic analysis of GC tissues at different stages.
  • Bioinformatic analyses including differential gene expression (DEG), cell-cell interaction, and pseudotime analyses.
  • Validation of DOT1L, CD44, and CTNNB1 expression and localization using immunofluorescence (IF).
  • TCGA and GTEx database analyses for gene expression and prognostic value verification.

Main Results

  • DOT1L expression was significantly increased in low-grade intraepithelial neoplasia (LGIN) and early gastric carcinoma (EGC) compared to normal tissues.
  • DOT1L expression correlated significantly with tumor mutational burden (TMB), microsatellite instability (MSI), and tumor proliferation index.
  • DOT1L was found to promote CD44 expression via the Wnt/β-catenin signaling pathway, enhancing stemness properties in GC.
  • DOT1L, CD44, and CTNNB1 (β-catenin) showed positive co-localization and correlation.

Conclusions

  • DOT1L is an important regulator of CSCs in GC, potentially crucial for coordinating lineage-specific gene expression during EMT.
  • DOT1L may serve as a potential therapeutic target for inhibiting GC stemness and progression.

Keywords:

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