In silico identification of miRNAs related to mitochondrial dysfunction in amyotrophic lateral sclerosis

Abstract

Non-coding, single-stranded RNA molecules known as microRNAs (miRNAs) regulate gene expression via mRNA degradation after transcription. As a result, they affect a number of pathways in organisms that are important for both health and disease. miRNAs can be utilized as potential diagnostic, prognostic, and therapeutic biomarkers for neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS). Neuronal cells are highly dependent on mitochondria, and mitochondrial dysfunction has been linked to neurodegenerative diseases. Pathological changes in ALS are associated with disruptions in mitochondrial structure, bioenergetics, and calcium homeostasis. In this study, we used an in silico approach to identify miRNAs associated with mitochondrial dysfunction in ALS based on target genes that are implied in both ALS and mitochondrial dysfunction. A literature search revealed the genes SOD1, FUS, TARDBP, C9orf72, CHCHD10, OPTN, VCP, TBK1 and BCL2 that cause mitochondrial dysfunction and are involved in the pathogenesis of ALS. Pathway enrichment analyses using Enrichr, g:Profiler, and CROssBAR tools confirmed that the identified genes have significant associations with ALS, mitochondrial dysfunction, and neuron differentiation. In silico miRNA predictions have been made using the databases miRWalk, miRTargetLink, TargetScan, and miRNet. A Venn diagram tool was used to select common miRNAs, and finally 28 miRNAs were discovered. One set of 28 miRNAs were subjected to set analysis using the miRNet and TAM tools for functional and enrichment analyses, respectively. In both databases, three common miRNAs, hsa-miR-9-5p, hsa-miR-141-3p and hsa-miR-125b, were found to be linked to ALS.