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Bioinformatic Analysis of microRNAs Associated with Chemotherapy-Induced Cognitive Impairment: Integration of Gene
Lucas Volpi Cândido1,2, Marcos Otávio Bueno1,2, Ricardo Cervini1,2
1Curso de Medicina, Universidade Alto Vale do Rio do Peixe (UNIARP), Caçador 89500-199, Brazil.
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.
Insights
MicroRNAs (miRNAs) are linked to chemotherapy-induced cognitive deficits, or chemobrain. Specific miRNAs like miR-155-5p, miR-21-5p, and miR-125b-5p are involved in neuroinflammation and synaptic dysfunction, offering potential therapeutic targets.
Area of Science:
- Neuroscience
- Molecular Biology
- Oncology
Background:
- Cancer treatments, particularly chemotherapy, cause significant neuropsychological changes.
- These cognitive deficits, termed chemobrain, present a persistent clinical challenge.
Purpose of the Study:
- Identify microRNAs (miRNAs) associated with chemotherapy-induced cognitive alterations.
- Map miRNA interaction networks and pinpoint involved biological pathways.
- Investigate the molecular mechanisms underlying chemobrain.
Main Methods:
- An integrative review of existing literature.
- In silico analysis of microRNA roles and interactions.
- Selection of six experimental studies using animal models.
Main Results:
- Chemotherapy agents (doxorubicin, cisplatin, methotrexate) induce deficits in memory, attention, and learning.
- miR-155-5p, miR-21-5p, and miR-125b-5p are implicated in neuroinflammation, oxidative stress, apoptosis, and synaptic dysfunction.
- miRNAs target key pathways including MAPK, PI3K-Akt, and mTOR, forming a network involved in cellular stress and neuroinflammation.
Conclusions:
- MicroRNAs play a crucial role in mediating chemotherapy-induced neurocognitive changes.
- These miRNAs represent potential biomarkers and therapeutic targets for mitigating chemobrain.
- Further research integrating molecular and behavioral data is needed for clinical applications.
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