Dottorato in NEUROSCIENZE CLINICO-SPERIMENTALI E PSICHIATRIA

Titolo della tesi: Extracellular vesicles-derived miR21 of non-tumoral origin as early diagnostic marker of glioma

Glioblastoma (GBM), the most aggressive and lethal form of brain tumors, is diagnosed only after the onset of severe symptoms, including headache, intracranial hypertension, weakness, motor deficits, seizures, or visual and speech disturbances. 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. Further analysis revealed that the early source of this marker is primarily non-tumor cells, particularly microglia. Conclusion. These observations point out the potential of miR21 as an early biomarker for glioma diagnosis and disease monitoring, thereby emphasizing the role of non-tumoral cells, particularly microglia, as rapidly reacting sentinels in the context of GBM.