Bioinformatic Analysis of microRNAs Associated with Chemotherapy-Induced Cognitive Impairment: Integration of Gene Networks and Neuroinflammatory Pathways

Background/Objectives: Neuropsychological changes induced by cancer and its treatments, especially chemotherapy, represent a significant clinical challenge, being responsible for persistent cognitive deficits known as chemobrain. This study aimed to identify microRNAs (miRNAs) associated with these alterations, map their interaction networks, and determine the main biological pathways involved. Methods: An integrative review and in silico analysis were conducted to study the role of microRNAs. Results: Six experimental studies using animal models were selected, which showed that agents such as doxorubicin, cisplatin, and methotrexate induce changes in domains such as memory, attention, and learning. Among the analyzed miRNAs, miR-155-5p, miR-21-5p, and miR-125b-5p stood out, being associated with pathways related to neuroinflammation, oxidative stress, apoptosis, and synaptic dysfunction. Computational analyses revealed that these miRNAs act on pathways such as MAPK, PI3K-Akt, mTOR, neurotrophins, and cytokine receptors. The interaction analysis among target genes also revealed a functionally connected network, with coordinated involvement in inflammation, neuronal apoptosis, and glial differentiation processes, suggesting a role in cellular stress responses and neuroinflammatory pathologies. Conclusions: These findings suggest that miRNAs play a central role in mediating the observed neurocognitive changes and may represent promising biomarkers and therapeutic targets to mitigate the effects of chemobrain. The study also highlights the need for future research integrating molecular and behavioral analyses to achieve more precise clinical applications.