Academic Journal
Cross-Species Identification of Urinary Small Extracellular Vesicle-Associated miR-223-3p as a Candidate Biomarker for Nephrolithiasis in a Discovery Cohort.
| Τίτλος: | Cross-Species Identification of Urinary Small Extracellular Vesicle-Associated miR-223-3p as a Candidate Biomarker for Nephrolithiasis in a Discovery Cohort. |
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| Συγγραφείς: | Chen BJ; Department of Urology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 60002, Taiwan., Uk JJ; Department of Urology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 60002, Taiwan., Shen CH; Department of Urology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 60002, Taiwan., Fang CY; Department of Medical Research, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 60002, Taiwan., Lai YY; Department of Urology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 60002, Taiwan., Hong YW; Department of Biochemical Science and Technology, National Chiayi University, Chiayi 60004, Taiwan., Eaw CY; Department of Biochemical Science and Technology, National Chiayi University, Chiayi 60004, Taiwan., Chuang MC; Department of Biochemical Science and Technology, National Chiayi University, Chiayi 60004, Taiwan., Chen JC; Department of Biochemical Science and Technology, National Chiayi University, Chiayi 60004, Taiwan. |
| Πηγή: | International journal of medical sciences [Int J Med Sci] 2026 Aug 24; Vol. 23 (10), pp. 3169-3182. Date of Electronic Publication: 2026 Aug 24 (Print Publication: 2026). |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Ivyspring International Publisher Country of Publication: Australia NLM ID: 101213954 Publication Model: eCollection Cited Medium: Internet ISSN: 1449-1907 (Electronic) Linking ISSN: 14491907 NLM ISO Abbreviation: Int J Med Sci Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Australia] : Ivyspring International Publisher, c2004- |
| Ιατρικοί όροι (MeSH): | MicroRNAs*/urine , MicroRNAs*/genetics , Nephrolithiasis*/urine , Nephrolithiasis*/genetics , Nephrolithiasis*/diagnosis , Nephrolithiasis*/pathology , Extracellular Vesicles*/genetics , Extracellular Vesicles*/metabolism, Biomarkers/urine ; Kidney/pathology ; Humans ; Animals ; Mice ; Female ; Male ; Disease Models, Animal ; Middle Aged ; Adult ; Gene Expression Profiling |
| Περίληψη: | Background: Nephrolithiasis remains a major global health burden with limited non-invasive tools for early diagnosis and monitoring. Urinary small extracellular vesicle (sEV)-associated microRNAs (miRNAs) are stable molecular signatures that reflect renal pathophysiological shifts. This study aims to identify candidate urinary sEV-associated miRNAs for nephrolithiasis in a clinical discovery cohort and prioritize candidate biomarkers by integrating human urinary sEV miRNA profiles with publicly available murine nephrolithiasis datasets. Methods: Small RNA sequencing was performed on RNA isolated from urinary sEVs obtained from a clinical discovery cohort (25 patients with nephrolithiasis and 8 healthy controls) to identify candidate biomarkers associated with nephrolithiasis. Differentially expressed miRNAs (DEmiRNAs) were identified using a |log₂ fold change| > 1 and adjusted P < 0.05 threshold. Functional enrichment (GO/KEGG) was conducted on predicted target genes. To prioritize biologically relevant candidates, human DEmiRNAs were intersected with an available murine kidney miRNA dataset (GSE186793) and the ExoCarta database. The lead candidate, miR-223-3p, was further validated via RT-qPCR in human urinary sEV samples and urinary sEVs isolated from an independent CaOx-induced mouse model. Results: We identified 111 significantly dysregulated urinary sEV-associated miRNAs (105 upregulated, 6 downregulated) in patients with nephrolithiasis. Functional analysis linked these miRNAs to endocytosis, mitochondrial organization, and the MAPK/Wnt signaling pathways. Integrative analysis of the human urinary sEV, the murine kidney miRNA datasets (GSE186793), and the ExoCarta database prioritized a conserved five-miRNA signature (miR-223-5p, miR-223-3p, miR-342-3p, let-7i-5p, and miR-29c-3p). Among these candidates, miR-223-3p demonstrated the strongest translational potential and was therefore selected for further validation. RT-qPCR confirmed that miR-223-3p was significantly upregulated in both human urinary sEVs and urinary sEVs from the CaOx-induced mouse model. Conclusion: Our findings characterize a distinct urinary sEVs-associated miRNA landscape within this discovery cohort and identify miR-223-3p as a promising candidate biomarker for nephrolithiasis. Given the relatively small, clinically heterogeneous discovery cohort and the absence of an independent validation cohort, these findings should be considered hypothesis-generating and require validation in larger, independent, clinically stratified prospective studies before clinical application. (© The author(s).) |
| Competing Interests: | Competing Interests: The authors declared that no know competing financial interests or personal relationships that could appeard to influence the work reported in this paper. |
| References: | Front Pharmacol. 2020 Jan 31;10:1655. (PMID: 32082158) Front Physiol. 2022 Aug 29;13:941143. (PMID: 36105281) Int J Mol Sci. 2025 Sep 05;26(17):. (PMID: 40943598) Biomed Pharmacother. 2024 Apr;173:116393. (PMID: 38461684) Shock. 2022 Mar 1;57(3):417-426. (PMID: 34710881) Biochim Biophys Acta Mol Cell Res. 2024 Jan;1871(1):119604. (PMID: 37806389) J Gerontol A Biol Sci Med Sci. 2024 Jul 1;79(7):. (PMID: 38447057) Nat Rev Nephrol. 2025 Nov;21(11):794-808. (PMID: 40790363) Oxid Med Cell Longev. 2021 Sep 2;2021:1676152. (PMID: 34512861) J Cell Physiol. 2019 May;234(5):5451-5465. (PMID: 30471116) Urology. 2022 Aug;166:104-110. (PMID: 35636636) Front Cell Dev Biol. 2020 Apr 15;8:244. (PMID: 32351960) Cell Mol Life Sci. 2024 Aug 25;81(1):369. (PMID: 39182194) Kidney360. 2023 Feb 1;4(2):245-257. (PMID: 36821616) J Proteomics. 2018 Aug 15;185:64-76. (PMID: 29953960) Inflamm Res. 2023 Mar;72(3):553-576. (PMID: 36640195) J Am Soc Nephrol. 2016 Jan;27(1):12-26. (PMID: 26251351) EBioMedicine. 2019 Jan;39:552-561. (PMID: 30467011) Ann Med Surg (Lond). 2024 Sep 10;86(10):5802-5810. (PMID: 39359758) Asian J Urol. 2018 Oct;5(4):205-214. (PMID: 30364478) Int J Biochem Cell Biol. 2022 Aug;149:106262. (PMID: 35787447) Int J Mol Sci. 2021 Jun 17;22(12):. (PMID: 34204452) Crit Rev Immunol. 2024;44(3):53-65. (PMID: 38421705) World J Urol. 2017 Sep;35(9):1301-1320. (PMID: 28213860) Nano Lett. 2023 Feb 22;23(4):1555-1563. (PMID: 36727669) Kaohsiung J Med Sci. 2024 Sep;40(9):789-800. (PMID: 39252576) J Cell Mol Med. 2019 Nov;23(11):7268-7278. (PMID: 31489770) Biochem Biophys Res Commun. 2023 Mar 12;648:50-58. (PMID: 36731227) Mol Biomed. 2025 Nov 17;6(1):110. (PMID: 41247622) |
| Contributed Indexing: | Keywords: Nephrolithiasis; Urinary small extracellular vesicle; biomarkers; microRNAs |
| Substance Nomenclature: | 0 (MicroRNAs) 0 (Biomarkers) 0 (MIR223, human) 0 (MIRN223 microRNA, mouse) |
| Entry Date(s): | Date Created: 20260929 Date Completed: 20260929 Latest Revision: 20260930 |
| Update Code: | 20260930 |
| PubMed Central ID: | PMC13617494 |
| DOI: | 10.7150/ijms.136918 |
| PMID: | 42807802 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1449-1907 |
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| DOI: | 10.7150/ijms.136918 |