Extracellular vesicle-derived miR21 of non-tumoral origin as early diagnostic marker of glioma

Background: Extracellular vesicles (EVs) are key elements in intercellular communication and are released into body fluids by all cells in physiological and pathological conditions. In brain tumors, EVs facilitate the bidirectional communication between neoplastic cells and the tumor microenvironment, promoting tumor progression and immune evasion. Among the various components of the EVs, microRNAs (miRs) act as potent regulators of gene expression. In particular, miR21 has gained attention as both a promising diagnostic biomarker and a key contributor to GBM progression. Methods: This study employed content analysis of miRs in EVs isolated from the brain, plasma, and urine of glioma-bearing mice. Results: Seven days after glioma cell injection, miR21 was the most highly expressed miR in both the brain and biofluids. Notably, its overexpression was particularly prominent in medium/large EVs. Co-culture experiments revealed that the early source of this marker is primarily microglia, rather than tumor cells. Conclusion: These data point out the potential of miR21 as early biomarker for glioma diagnosis and disease monitoring, emphasizing the role of non-tumoral cells, particularly microglia, as rapidly reacting elements in the context of gliomas.