Tumor-Educated Extracellular Vesicle-Derived LINC01116 Drives Non-Small Cell Lung Cancer Progression and Immunosuppression by Sponging miR-3614-5p to Upregulate ARHGAP1.

[OBJECTIVE] To investigate the role of extracellular vesicle (EV)-derived long non-coding RNA (lncRNA) in non-small cell lung cancer (NSCLC) progression and the tumor immune microenvironment.

[METHODS] Bioinformatic analyses of TCGA data identified an eight-lncRNA prognostic signature, including LINC01116. A LINC01116-centered ceRNA network was constructed. EVs from NSCLC patient blood were isolated. Functional effects were assessed using in vitro proliferation, migration, invasion, and macrophage polarization assays, and in vivo mouse models. Molecular interactions were validated by RNA pull-down, RIP, and luciferase assays.

[RESULTS] LINC01116 was upregulated in NSCLC tissues and EVs. It functioned as a ceRNA by sponging miR-3614-5p, leading to upregulation of ARHGAP1. Single-cell RNA-seq revealed LINC01116 expression in epithelial cells and macrophages. EV-transferred LINC01116 promoted NSCLC cell malignancy, induced macrophage M2 polarization, and accelerated tumor growth and metastasis in vivo via the miR-3614-5p/ARHGAP1 axis.

[CONCLUSION] EV-derived LINC01116 promotes NSCLC progression and immunosuppression via the miR-3614-5p/ARHGAP1 pathway, presenting a novel prognostic and therapeutic target.