In vitro evidence that perampanel modulates miR-21-5p and miR-29a-3p associated with anti-glioma effects

Perampanel (PER), a selective AMPA receptor antagonist, has shown anti-seizure activity and has been proposed to exert anti-glioma effects. However, the molecular pathways underlying these effects in glioma remain poorly characterized. In this in vitro study, we investigated the effects of PER on microRNA (miRNA) expression in two glioblastoma cell lines (U87 and U138) and in patient-derived glioma stem cell (GSC) neurospheres. PER treatment was associated with a distinct miRNA expression profile, including the downregulation of miR-21-5p and miR-29a-3p. These miRNAs have been previously implicated in glioma cell proliferation, migration, and epithelial–mesenchymal transition (EMT)-related pathways. Functional assays showed that overexpression of miR-21-5p and miR-29a-3p increased migratory capacity and induced morphological changes consistent with a more motile phenotype. PER exposure was associated with attenuation of these phenotypic changes. In addition, PER reduced cell viability in glioblastoma cell lines and decreased neurosphere size in GSC cultures, accompanied by reduced miR-21-5p expression. These findings suggest that PER is associated with modulation of miRNAs involved in migratory and EMT-related phenotypes in glioma cells in vitro. While the data do not demonstrate direct inhibition of EMT or tumor progression, they provide preliminary insight into potential molecular pathways linked to PER exposure and support further mechanistic and in vivo studies.