DOI: 10.1002/tox.23862 ISSN: 1520-4081

Tumor‐derived exosome ElNF1‐AS1 affects the progression of gastric cancer by promoting M2 polarization of macrophages

Bo Ma, Jun Wang, Paheredini Yusufu
  • Health, Toxicology and Mutagenesis
  • Management, Monitoring, Policy and Law
  • Toxicology
  • General Medicine
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Abstract

Background

This study attempted to investigate the role of exosome ELFN1‐AS1 in gastric cancer (GC).

Methods

The study used various techniques to determine the level of exosomal ELFN1‐AS1 in GC tissue and cells, including quantitative real‐time PCR. Pull‐down assay and dual‐luciferase reporter assay were employed to identify interactions between ELFN1‐AS1 and miR‐4644, as well as miR‐4644 and PKM. Western blot was employed to explore the potential regulatory mechanism. Several in vitro assays were conducted in xenograft models to investigate the impacts of exosomal ELFN1‐AS1 on GC development, metastasis and macrophage polarization.

Results

ELFN1‐AS1 was upregulated in GC tissue and cells, with high enrichment in GC‐derived exosomes. Exosomal ELFN1‐AS1 enhances the cell abilities and stemness of GC. ELFN1‐AS1 targeted and regulated miR‐4644, which triggered PKM expression. Exosomal ELFN1‐AS1 modulated glycolysis via PKM in an HIF‐1α dependent manner in GC, promoting M2 polarization and macrophage recruitment. Furthermore, exosomal ELFN1‐AS1 enhanced GC cell growth, metastasis and M2 polarization in vivo.

Conclusions

The study suggests that ELFN1‐AS1 could be a promising biomarker for the diagnosis and treatment of GC.

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