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

## TL;DR

This paper explores how certain microRNAs are linked to cognitive issues caused by chemotherapy, suggesting they could be used as biomarkers or treatment targets.

## Contribution

The study identifies specific miRNAs and their associated pathways involved in chemotherapy-induced cognitive impairment, offering new insights into potential therapeutic strategies.

## Key findings

- miR-155-5p, miR-21-5p, and miR-125b-5p are associated with neuroinflammation and cognitive dysfunction pathways.
- These miRNAs interact with pathways like MAPK, PI3K-Akt, and mTOR, which are involved in cellular stress and inflammation.
- The miRNAs form a functionally connected network related to neuronal apoptosis and glial differentiation.

## Abstract

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.