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Review
. 2024 Mar 20;14(3):377.
doi: 10.3390/biom14030377.

Sporadic Amyotrophic Lateral Sclerosis Skeletal Muscle Transcriptome Analysis: A Comprehensive Examination of Differentially Expressed Genes

Elisa Gascón  1   2   3   4 , Pilar Zaragoza  1   2   3   4 , Ana Cristina Calvo  1   2   3   4 , Rosario Osta  1   2   3   4
Affiliations
Review

Sporadic Amyotrophic Lateral Sclerosis Skeletal Muscle Transcriptome Analysis: A Comprehensive Examination of Differentially Expressed Genes

Elisa Gascón et al. Biomolecules. .

Abstract

Amyotrophic lateral sclerosis (ALS) that comprises sporadic (sALS) and familial (fALS) cases, is a devastating neurodegenerative disorder characterized by progressive degeneration of motor neurons, leading to muscle atrophy and various clinical manifestations. However, the complex underlying mechanisms affecting this disease are not yet known. On the other hand, there is also no good prognosis of the disease due to the lack of biomarkers and therapeutic targets. Therefore, in this study, by means of bioinformatics analysis, sALS-affected muscle tissue was analyzed using the GEO GSE41414 dataset, identifying 397 differentially expressed genes (DEGs). Functional analysis revealed 320 up-regulated DEGs associated with muscle development and 77 down-regulated DEGs linked to energy metabolism. Protein-protein interaction network analysis identified 20 hub genes, including EIF4A1, HNRNPR and NDUFA4. Furthermore, miRNA target gene networks revealed 17 miRNAs linked to hub genes, with hsa-mir-206, hsa-mir-133b and hsa-mir-100-5p having been previously implicated in ALS. This study presents new potential biomarkers and therapeutic targets for ALS by correlating the information obtained with a comprehensive literature review, providing new potential targets to study their role in ALS.

Keywords: amyotrophic lateral sclerosis (ALS); bioinformatics; extracellular/circulating biomarkers; microRNA; neurodegenerative diseases (NDDs).

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Volcano plot of differentially expressed genes (DEGs). Red dots represent up-regulated genes according to p-values < 0.05 and |logFC| > 0.5. Blue dots represent down-regulated genes according to p-values < 0.05 and |logFC| < 0.5.
Figure 2
Figure 2
Gene Ontology (GO) function and pathway enrichment analysis of up-regulated DEGs and down-regulated DEGs. The top 10 terms for each of the GO analysis categories’ biological processes (BPs), cellular component (CC) and molecular function (MF) are presented. (a) BPs of up-regulated DEGs; (b) CC of up-regulated DEGs; (c) MF of up-regulated DEGs; (d) BPs of down-regulated DEGs; (e) CC of down-regulated DEGs; and (f) MF of down-regulated DEGs.
Figure 2
Figure 2
Gene Ontology (GO) function and pathway enrichment analysis of up-regulated DEGs and down-regulated DEGs. The top 10 terms for each of the GO analysis categories’ biological processes (BPs), cellular component (CC) and molecular function (MF) are presented. (a) BPs of up-regulated DEGs; (b) CC of up-regulated DEGs; (c) MF of up-regulated DEGs; (d) BPs of down-regulated DEGs; (e) CC of down-regulated DEGs; and (f) MF of down-regulated DEGs.
Figure 3
Figure 3
Analysis of differentially expressed gene (DEG) networks. (a) MCODE-clustered subnetwork of up-regulated DEGs. (b) MCODE-clustered subnetwork of down-regulated DEGs.
Figure 4
Figure 4
Enrichment analysis of MCODE-clustered subnetwork of up-regulated DEGs by Metascape.
Figure 5
Figure 5
Enrichment analysis of MCODE-clustered subnetwork of down-regulated DEGs by Metascape.
Figure 6
Figure 6
Hub genes identified by cytoHubba. (a) Hub genes of the PPI network of up-regulated DEGs. (b) Hub genes of the PPI network of down-regulated DEGs.
See this image and copyright information in PMC

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