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Identification of an exosomal miRNA-mRNA regulatory network contributing to methotrexate efficacy.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2024 Jun 30; Vol. 135, pp. 112280. Date of Electronic Publication: 2024 May 21. - Publication Year :
- 2024
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Abstract
- Objective: Methotrexate (MTX) is an economic and effective medicine treatment for psoriasis. Extracellular vesicle (EV) miRNA biomarkers related to its efficiency have been identified in various diseases. Whether certain miRNA profiles are associated with psoriasis treatment is unknown. In order to determine specific miRNA biomarkers for MTX effectiveness prediction and the severity of psoriasis, our study looked at the variations in circulating EV miRNA profiles before and after MTX therapy.<br />Methods: Plasma EV isolation and next-generation sequencing were performed to identify differentially expressed EV miRNAs between GRs (n = 14) and NRs (n = 6). Univariate and multiple linear regression analyses were performed to evaluate the correlation between PASI scores and miRNA expression levels.<br />Results: 15 miRNAs out of a total profile of 443 miRNAs were substantially different between GRs and NRs at baseline, 4 of them (miR-199a-5p, miR-195-5p, miR-196a-5p, and miR-1246) have the potential to distinguish between GRs and NRs [area under the curve (AUC) ≥ 0.70, all P < 0.05]. KEGG pathway analyses revealed differentially expressed miRNAs to potentially target immune-related pathways. SIRT1 was discovered to be a target of miR-199a-5p and involved in MAPK signaling pathway. MiR-191-5p and miR-21-5p expression levels have been discovered to positively correlate with PASI scores[P < 0.05].<br />Conclusion: This pilot investigation found that miR-199a-5p, miR-195-5p, miR-196a-5p, and miR-1246 might be prospective biomarkers to predict the efficacy of MTX, and that miR-191-5p and miR-21-5p were correlated with psoriasis severity. Five of them previously reported to be involved in MAPK signaling pathway, indicating a potential role of MTX in delaying the progression of psoriatic inflammation.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Male
Female
Adult
Middle Aged
Gene Regulatory Networks
RNA, Messenger metabolism
RNA, Messenger genetics
Biomarkers
Sirtuin 1 genetics
Sirtuin 1 metabolism
Treatment Outcome
Methotrexate therapeutic use
Methotrexate pharmacology
MicroRNAs genetics
MicroRNAs metabolism
Psoriasis drug therapy
Psoriasis genetics
Exosomes metabolism
Exosomes genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 135
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 38776848
- Full Text :
- https://doi.org/10.1016/j.intimp.2024.112280