LncRNA GAS5 inhibits the remodeling of the tumor microenvironment by binding to miR-93-5p, thereby suppressing the development of osteosarcoma.

Abstract

The inflammatory tumor immune microenvironment is being increasingly recognized as a key driver of osteosarcoma (OS) progression; however, the molecular mechanisms linking long noncoding RNAs (lncRNAs) to inflammasome signaling in OS remain poorly understood. In this study, we investigated the role of growth arrest-specific transcript 5 (GAS5) in regulating inflammatory remodeling and tumor development. We found that GAS5 expression was significantly decreased in osteosarcoma cells, whereas miR-93-5p expression was upregulated, indicating a potential inverse regulatory relationship. Mechanistically, GAS5 functioned as a competing endogenous RNA for miR-93-5p, thereby alleviating miR-93-5p-mediated downregulation of the E3 ubiquitin ligase TRIM31. Restoration of TRIM31 expression promoted NLRP3 protein turnover and attenuated inflammasome activation, as evidenced by reduced cleaved caspase-1, GSDMD-N, and IL-18 secretion. Functionally, GAS5 overexpression suppressed inflammatory cytokine production and limited protumorigenic inflammatory remodeling, ultimately inhibiting osteosarcoma cell progression. Collectively, our findings reveal a novel GAS5/miR-93-5p/TRIM31/NLRP3 regulatory axis that connects lncRNA-mediated posttranscriptional control to inflammasome signaling in osteosarcoma, providing new mechanistic insight and a potential therapeutic framework for targeting inflammation-associated OS progression.