MicroRNA-Mediated regulation of GFAP as a marker of astrocyte reactivity: An in silico study

Abstract

Astrocytic reactivity is characterized by profound cytoskeletal remodeling, altered proteostasis, and elevated expression of glial fibrillary acidic protein (GFAP), a hallmark intermediate filament of reactive astrocytes. Rather than being regulated as an isolated molecular target, GFAP expression reflects the broader structural and stress-adaptive state of astrocytes. In this study, we employed an integrative in silico framework to identify microRNAs (miRNAs) potentially associated with astrocytic cytoskeletal and proteostatic gene networks in which GFAP serves as a structural marker of reactive astrocyte phenotypes. Protein–protein interaction analysis was used to define a GFAP-associated protein set, followed by multi-database miRNA target prediction and network-level prioritization. Ten candidate miRNAs were identified, with hsa-miR-1207-5p emerging as a broadly predicted multi-target miRNA within the GFAP-associated network. Functional enrichment analysis highlighted intermediate filament organization and suggested a potential involvement of chaperone-mediated protein quality control mechanisms. Collectively, these findings propose a network-level miRNA-associated framework relevant to reactive astrocyte biology, in which GFAP functions as a structural indicator rather than a direct regulatory endpoint, and provide a rational basis for experimental validation.