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

Abstract

This study attempted to investigate the role of exosome ELFN1-AS1 in gastric cancer (GC). 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. 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. The study suggests that ELFN1-AS1 could be a promising biomarker for the diagnosis and treatment of GC.