Identifying miRNAs associated with amyotrophic lateral sclerosis and mitochondrial dysfunction through bioinformatics approaches

Abstract

Objectives: MicroRNAs (miRNAs) are non-coding RNA molecules that control gene expression by causing messenger RNA to degrade after transcription. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that involves the gradual deterioration and death of motor neurons, resulting in muscle weakness, paralysis, and eventual fatality. A prominent feature of ALS is the presence of mitochondrial dysfunction. The identification of miRNAs associated with mitochondrial dysfunction in ALS through in silico approaches can offer valuable insights into underlying processes and targets for therapeutic interventions. Methods: Computational tools and publicly available databases were employed for the purpose of identifying specific miRNAs that could potentially play a role in the onset or progression of mitochondrial dysfunction in ALS. Results: A review of the literature revealed that the genes SOD1, coiled-coil-helix-coiled-coil-helix domain-containing protein 10, C9orf72, OPTN, valosin-containing protein, TARDBP, TBK1, FUS, and BCL2 are linked to mitochondrial dysfunction and are involved in the etiology of ALS. Enrichment analyses of biological pathways performed with the computational tools Enrichr, g: Profiler, and CROssBAR confirmed that the discovered genes are strongly related to ALS, mitochondrial failure, and differentiation of neurons. Furthermore, miRNA computational predictions were performed utilizing the publicly available databases miRTargetLink, miRNet, miRWalk, and TargetScan. To identify common miRNAs, a Venn diagram was used, and 28 miRNAs were selected as a result. For further analysis, a set of 28 miRNAs was subjected to functional and enrichment studies using the computational programs miRNet and TAM, respectively. Results from both computational programs consistently revealed that the miRNAs hsa-miR-125b, hsa-miR-9-5p, and hsa-miR-141-3p were related to ALS. Conclusion: We proved that in silico approaches projected the effects of miR-9, miR-141, and miR-125b targeting the identified genes on ALS, and we demonstrated that the genes involved in mitochondrial dysfunction in ALS are based on the literature.