The Novel Regulatory Role of lncRNA-miRNA-mRNA Axis in Amyotrophic Lateral Sclerosis: An Integrated Bioinformatics Analysis

Abstract

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that primarily affects motor neurons, causing muscle atrophy, bulbar palsy, and pyramidal tract signs. However, the aetiology and pathogenesis of ALS have not been elucidated to date. In this study, a competitive endogenous RNA (ceRNA) network was constructed by analyzing the expression profiles of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) that were matched by 7 ALS samples and 4 control samples, and then a protein-protein interaction (PPI) network was constructed to identify the genes related to ALS. Gene Ontology (GO) was used to study the potential functions of differentially expressed mRNAs (DEmRNAs) in the ceRNA network. For the ALS and control groups, 247177 potential lncRNA-mRNA ceRNA relationship pairs were screened. Analysis of significant relationship pairs demonstrated that the PPI modules formed by the MALAT1-regulated SYNRG, ITSN2, PICALM, AP3B1, and AAK1 genes may play important roles in the pathogenesis of ALS, and these results may help to characterize the pathogenesis of ALS.

Deregulation of ncRNA in Neurodegenerative Disease: Focus on circRNA, lncRNA and miRNA in Amyotrophic Lateral Sclerosis

“…This model allows assessing how the different ncRNAs can interact together and affect the molecular pathogenesis of disease (Sardina et al, 2017). On this subject, Liu et al (2021) created a ceRNA network with the aim of making a molecular characterization of the ALS development and providing promising targets for clinical treatment. The study made it possible to understand that the regulation of MALAT1 plays an important role in the development of the disease.…”

“…In this context, it is important to note that recent studies showed that lncRNA and mRNA can compete for binding to miRNAs and this interaction can play a role in different diseases, including ALS ( Liu et al, 2021 ). The potential cross-talk between miRNA-lncRNA-mRNA can be investigated by means of competitive endogenous RNA (ceRNA) network analysis.…”

“…Furthermore, the SYNRG , ITSN2 , AAK1 , PICALM and AP3B1 genes associated with ALS and regulated by MALAT1, have been found to play an important role in the pathogenesis of ALS. In particular, the discovery of the association between AAK1 gene and ALS is of considerable interest, although further research is necessary to understand the correlation of this gene and the other ones with the disease ( Liu et al, 2021 ).…”

“…In addition, miRNAs have been found to exert a function in neuronal inflammation in ALS ( Emde et al, 2015 ). Numerous works showed that miRNAs in affected subjects can cross the blood-brain barrier to reach the bloodstream and, thereby, could be utilized as biomarkers of disease ( Saucier et al, 2019 ; Liu et al, 2021 ). Highly deregulated miRNAs have been associated with different degrees of disease progression.…”

RNA Deregulation in Amyotrophic Lateral Sclerosis: The Noncoding Perspective

“…Bioinformatics analyses and computational studies highlighted the importance of unraveling altered gene pathways in ALS [ 95 , 96 , 97 , 98 , 99 ]. Concordantly, several efforts were made to match and functionally link miRNAs and their target genes through integrative approaches in ALS-associated model systems.…”