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PiRNA and miRNA Can Suppress the Expression of Multiple Sclerosis Candidate Genes.

ABSTRACT: Multiple sclerosis (MS) is a common inflammatory demyelinating disease with a high mortality rate. MS is caused by many candidate genes whose specific involvement has yet to be established. The aim of our study was to identify endogenous miRNAs and piRNAs involved in the regulation of MS candidate gene expression using bioinformatic methods. A program was used to quantify the interaction of miRNA and piRNA nucleotides with mRNA of the target genes. We used 7310 miRNAs from three databases and 40,000 piRNAs. The mRNAs of the candidate genes revealed miRNA binding sites (BSs), which were located separately or formed clusters of BSs with overlapping nucleotide sequences. The miRNAs from the studied databases were generally bound to mRNAs in different combinations, but miRNAs from only one database were bound to the mRNAs of some genes. For the first time, a direct interaction between the complete sequence of piRNA nucleotides and the nucleotides of their mRNA BSs of target genes was shown. One to several clusters of BSs of miRNA and piRNA were identified in the mRNA of ADAM17, AHI1, CD226, EOMES, EVI5, IL12B, IL2RA, KIF21B, MGAT5, MLANA, SOX8, TNFRSF1A, and ZBTB46 MS candidate genes. These piRNAs form the expression regulation system of the MS candidate genes to coordinate the synthesis of their proteins. Based on these findings, associations of miRNAs, piRNAs, and candidate genes for MS diagnosis are recommended.

SUBMITTER: Kamenova S

PROVIDER: S-EPMC9823834 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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piRNA and miRNA Can Suppress the Expression of Multiple Sclerosis Candidate Genes.

Kamenova Saltanat S Sharapkhanova Aksholpan A Akimniyazova Aigul A Kuzhybayeva Karlygash K Kondybayeva Aida A Rakhmetullina Aizhan A Pyrkova Anna A Ivashchenko Anatoliy A

Nanomaterials (Basel, Switzerland) 20221221 1

Multiple sclerosis (MS) is a common inflammatory demyelinating disease with a high mortality rate. MS is caused by many candidate genes whose specific involvement has yet to be established. The aim of our study was to identify endogenous miRNAs and piRNAs involved in the regulation of MS candidate gene expression using bioinformatic methods. A program was used to quantify the interaction of miRNA and piRNA nucleotides with mRNA of the target genes. We used 7310 miRNAs from three databases and 40 ...[more]

PMID: 36615932

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Project description:IntroductionMultiple sclerosis (MS) is a chronic and debilitating inflammatory disease of the central nervous system (CNS), characterized by demyelination and neurodegeneration. Emerging evidence implicates neutrophils in MS pathogenesis, particularly through processes like neutrophil extracellular traps (NETs) formation and degranulation, which may exacerbate inflammation and autoimmunity.MethodsRNA sequencing of peripheral blood neutrophils from MS patients and healthy controls identified differentially expressed genes (DEGs). Pathway enrichment and protein-protein interaction (PPI) analyses highlighted potential biomarkers, validated using reverse transcription quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA).ResultsOur analysis identified 1,968 DEGs in neutrophils from MS patients, comprising 1,068 upregulated and 900 downregulated genes. Pathway enrichment analysis revealed significant involvement of immune processes, including antigen presentation, B and T cell receptor signaling, intracellular signaling cascades, and neutrophil degranulation. Notably, KEGG analysis highlighted a pivotal role for upregulated genes in neutrophil extracellular traps (NETs) formation, a process increasingly associated with autoimmunity. PPI network analysis pinpointed five key hub genes-LCN2, LTF, ELANE, CAMP, and CTSG-as central players in neutrophil-mediated immune modulation. Protein-level validation using ELISA confirmed elevated levels of LCN2, ELANE, CAMP, and CTSG, consistent with transcriptomic findings, further supporting their role as biomarkers. Subsequent RT-qPCR validation demonstrated robust diagnostic potential for these genes, with area under the curve (AUC) values of 0.952 (LCN2), 0.827 (LTF), 0.968 (ELANE), 0.950 (CAMP), and 0.862 (CTSG).DiscussionThese findings uncover a previously underappreciated role for neutrophils in MS pathogenesis, driven by alterations in gene expression linked to immune modulation and NET formation. The identified biomarkers, particularly ELANE and LCN2, demonstrate strong diagnostic potential, offering a new avenue for non-invasive MS diagnostics. Beyond clinical utility, this study highlights the importance of neutrophil-driven immune responses in MS, providing mechanistic insights into the complex interplay between innate and adaptive immunity in demyelinating diseases. Furthermore, these findings suggest that targeting neutrophil-specific processes, such as NETs formation and degranulation, could mitigate inflammatory damage and provide novel therapeutic approaches for MS treatment. These results lay the groundwork for future studies exploring therapeutic strategies targeting neutrophil functions in MS.

Dataset Information

PiRNA and miRNA Can Suppress the Expression of Multiple Sclerosis Candidate Genes.

Publications

piRNA and miRNA Can Suppress the Expression of Multiple Sclerosis Candidate Genes.

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