In silico prediction of miRNAs targetingchemotherapy related cognitive impairment associatedgenes; the first step towards the utilization of RNAi againstcancer therapy side effects

Introduction: Chemobrain or Chemotherapy related cognitiveimpairment (CRCI) is a chemotherapy side effect experiencedby many cancer patients. The specific molecular mechanismsbehind this phenomenon are still largely undetermined. miRNAsas a class of non-coding RNAs fine-tune gene expressionby interacting with the ۳' untranslated region of target mRNAs.While miRNAs are emerging as putative therapeutic targets invarious neurocognitive disorders, their implication in CRCI remainsminimally understood.Materials and Methods: We utilized two major miRNAmRNAinteraction prediction tools, targetscan and miRwalkto predict miRNA-target interaction. We predicted miRNAsinteractions with genes that participated in CRCI pathogenesis.CRCI genes were extracted from ۲ microarray studies(۱۰.۳۳۹۰/ijms۲۱۰۵۱۸۶۷ & ۱۰.۱۰۱۶/j.exger.۲۰۲۱.۱۱۱۴۵۱). onlygenes with |LogFC|>۰.۲ and p value<۰.۵ were included in theanalysis, accounting for ۱۴۲ genes upregulated and ۲۰۳ downregulated.Results: Functional enrichment revealed that the major functionsassociated with these genes are cancer, neurodegenerativediseases, and addiction. We identified ۴۵ miRNAs predicted tointeract with downregulated mRNAs with a possible inductiveeffect on CRCI mechanisms and ۱۵ miRNAs connected withupregulated genes with a possible inhibitory effect on majormRNAs perturbated in CRCI. Among these miRNAs, miR۲۹a-۳p, miR۲۹c-۳p, and miR۲۴-۳p were predicted to interact with ۳genes. We also retrieved the proposed binding sites for miRNAson target mRNAs via miRWalk, which promisingly can be utilizedfor designing RNAi tools to target such genes.Conclusion: Our findings suggest a set of promising therapeutictargets among both mRNAs and miRNAs that potentiallycan be targeted via RNAi strategies to ameliorate cancer treatment-induced neurotoxicity and thus cognitive impairment.