NEAT1 in bone marrow mesenchymal stem cell-derived extracellular vesicles promotes melanoma by inducing M2 macrophage polarization

Bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) reportedly play an important role in melanoma pathogenesis. This study aimed to explore the mechanisms of EVs-carried long non-coding RNA (lncRNA) NEAT1 involvement in melanoma. Gain- and loss-of-function experiments were performed to determine biological characteristics of A-375 melanoma cells. Bioinfomatic prediction, RNA immunoprecipitation (RIP), and dual luciferase reporter gene experiments were applied to investigate the roles of NEAT1 and microRNA-374a-5p (miR-374a-5p), and leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4). A subcutaneous tumor model was constructed using nude mice, and in vivo fluorescence imaging was used to observe the effect of NEAT1 on the growth and metastasis of melanoma cells in vivo. The results indicated that BMSC-EVs could be internalized by macrophages to promote the expression of macrophages M2 markers. M2 type macrophages promoted malignancy of melanoma cells. NEAT1 derived from BMSC-EVs promoted the progression of melanoma by promoting M2 polarization of macrophages. NEAT1 inhibits miR-374 expression, while miR-374 could upregulate LGR4-dependent IQGAP1 expression. The tumor-inhibiting effect of NEAT1 silencing was validated in the nude mouse xenograft model. Collectively, the results demonstrated that BMSC-EVs carrying NEAT1 can promote the progression of melanoma by inducing M2 polarization of macrophages, and thus may be considered as a potential target for melanoma therapeutics.