LncRNA LUCAT1 and exosomal MIF induced by Helicobacter pylori promotes M2 macrophage polarization in gastric cancer

BACKGROUND AND AIMS Helicobacter pylori ( H. pylori ), particularly cytotoxin-associated gene A (CagA)-positive strains, play a crucial role in gastric cancer (GC) pathogenesis. Long noncoding RNAs (lncRNAs) are emerging as key regulators of cancer progression; however, their involvement in H. pylori -induced GC remains unclear. METHODS RNA sequencing was performed on GC and normal cells exposed to H. pylori . LncRNA expression changes were analyzed, and key candidates were validated using functional assays. RESULTS RNA-seq analysis revealed the significant upregulation of specific lncRNAs, such as LUCAT1 in AGS cells and SNHG1 and SNHG15 in GES-1 cells, primarily influenced by CagA-positive H. pylori infection. LUCAT1 expression was notably higher in GC tissues with CagA-positive H. pylori than in negative samples. LUCAT1 regulates MIF expression via H3K27 acetylation mediated by its interaction with HDAC1/2. Exosomal MIF derived from H. pylori -infected GC cells promotes M2 macrophage polarization via the PTEN/PI3K/AKT pathway, contributing to increased GC cell proliferation and metastasis. These findings underscore the profound impact of H. pylori infection on the tumor microenvironment through lncRNA expression and exosome-mediated signaling regulation, highlighting the pivotal role of lncRNA-driven mechanisms in GC progression. CONCLUSIONS Our study offers an opportunity to explore therapeutic strategies that target lncRNA modulation and exosomal signaling in H. pylori rather than focusing solely on its complete eradication.