Extracellular vesicle-derived LINC00482 induces microglial M2 polarization to facilitate brain metastasis of NSCLC

Considering the crucial role of long non-coding RNAs (lncRNAs) in non-small cell lung cancer (NSCLC), we tried to analyze the role of extracellular vesicle (EV)-derived LINC00482 in the occurrence of brain metastasis in NSCLC. LINC00482 expression was quantified in EVs isolated from serum samples of NSCLC patients (serumEVs). Ectopic expression and depletion assays were conducted in the microglial cell line HMC3 co-cultured with serum-EVs and in xenograft mouse models of NSCLC to explore the roles of EV-carried LINC00482. LINC00482 was enriched in serum-EVs and induced M2 polarization of microglial cells HMC3 in vitro. LINC00482 competitively bound to miR-142-3p and upregulated the expression of miR-142-3p target gene TGF-beta 1 in HMC3 cells, thus promoting microglial M2 polarization. EV-derived LINC00482-induced M2 microglia promoted the malignant properties of NSCLC cells. In vivo data demonstrated that EVs transmitted LINC00482 to regulate the miR-142-3p/TGF-beta 1 axis, induce microglial M2 polarization and affect the pre-metastatic niche, thus enhancing brain metastasis of NSCLC. Overall, suppression of the expression of tumor-derived LINC00482 or LINC00482containing EVs, may serve as an effective target for contributing to the reduction of brain metastasis of NSCLC.