LncRNA NEAT2 regulates the inflammatory microenvironment of gastric cancer by miR-155- 5p/SOCS1 pathway

Abstract Aberrantly activated inflammatory microenvironment and tumor metastasis are core drivers of gastric cancer progression. Whether lncRNA NEAT2 exhibits distinct expression profiles and holds prognostic value in gastric cancer constituted the central question of the current work, explore its regulatory effects on invasion, migration and inflammatory response of gastric cancer cells was the aim, to offer novel molecular targets applicable to the diagnosis and targeted treatment of gastric cancer, the mechanistic basis through which the NEAT2/miR-155-5p/SOCS1 axis drives gastric cancer malignant progression was clarified. TCGA database analysis revealed that the homologous gene NEAT2 was significantly upregulated in gastric cancer tissues, and patients with high NEAT2 expression exhibited better overall survival. The serum NEAT2 level in gastric cancer patients was substantially upregulated compared with the normal control group, and NEAT2 expression gradually decreased with advancing tumor stage from I-II to III-IV. Consistently, NEAT2 expression remained markedly elevated in gastric cancer cell lines. It verified that NEAT2 silencing remarkably suppressed the migratory and invasive capacities of gastric cancer cells. Mechanistically, NEAT2 acted as an endogenous molecular sponge to targetedly repress miR-155-5p, suppress SOCS1 and subsequently activate the TLR4/NF-κB inflammatory signaling cascade to exacerbate local inflammation. NEAT2 is abnormally overexpressed in gastric cancer and participates in remodeling the tumor inflammatory microenvironment and facilitating malignant progression. The NEAT2/miR-155-5p/SOCS1 ceRNA axis holds great potential for non‑invasive diagnosis and targeted therapy of gastric cancer.