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Cross-Species Identification of Urinary Small Extracellular Vesicle-Associated miR-223-3p as a Candidate Biomarker for Nephrolithiasis in a Discovery Cohort.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Cross-Species Identification of Urinary Small Extracellular Vesicle-Associated miR-223-3p as a Candidate Biomarker for Nephrolithiasis in a Discovery Cohort.
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
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  Data: 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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  Data: &lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Chen+BJ%22&quot;&gt;Chen BJ&lt;/searchLink&gt;; Department of Urology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 60002, Taiwan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Uk+JJ%22&quot;&gt;Uk JJ&lt;/searchLink&gt;; Department of Urology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 60002, Taiwan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Shen+CH%22&quot;&gt;Shen CH&lt;/searchLink&gt;; Department of Urology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 60002, Taiwan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Fang+CY%22&quot;&gt;Fang CY&lt;/searchLink&gt;; Department of Medical Research, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 60002, Taiwan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Lai+YY%22&quot;&gt;Lai YY&lt;/searchLink&gt;; Department of Urology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 60002, Taiwan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Hong+YW%22&quot;&gt;Hong YW&lt;/searchLink&gt;; Department of Biochemical Science and Technology, National Chiayi University, Chiayi 60004, Taiwan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Eaw+CY%22&quot;&gt;Eaw CY&lt;/searchLink&gt;; Department of Biochemical Science and Technology, National Chiayi University, Chiayi 60004, Taiwan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Chuang+MC%22&quot;&gt;Chuang MC&lt;/searchLink&gt;; Department of Biochemical Science and Technology, National Chiayi University, Chiayi 60004, Taiwan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Chen+JC%22&quot;&gt;Chen JC&lt;/searchLink&gt;; Department of Biochemical Science and Technology, National Chiayi University, Chiayi 60004, Taiwan.
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– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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.&lt;br /&gt;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| &gt; 1 and adjusted P &amp;lt; 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.&lt;br /&gt;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.&lt;br /&gt;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.&lt;br /&gt; (&#169; The author(s).)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: 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.
– Name: Ref
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  Label: Update Code
  Group: Date
  Data: 20260930
– Name: PubmedCentralID
  Label: PubMed Central ID
  Group: ID
  Data: PMC13617494
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.7150/ijms.136918
– Name: AN
  Label: PMID
  Group: ID
  Data: 42807802
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42807802
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.7150/ijms.136918
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 3169
    Subjects:
      – SubjectFull: Biomarkers urine
        Type: general
      – SubjectFull: Kidney pathology
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Female
        Type: general
      – SubjectFull: Male
        Type: general
      – SubjectFull: Disease Models, Animal
        Type: general
      – SubjectFull: Middle Aged
        Type: general
      – SubjectFull: Adult
        Type: general
      – SubjectFull: Gene Expression Profiling
        Type: general
      – SubjectFull: MicroRNAs urine
        Type: general
      – SubjectFull: MicroRNAs genetics
        Type: general
      – SubjectFull: Nephrolithiasis urine
        Type: general
      – SubjectFull: Nephrolithiasis genetics
        Type: general
      – SubjectFull: Nephrolithiasis diagnosis
        Type: general
      – SubjectFull: Nephrolithiasis pathology
        Type: general
      – SubjectFull: Extracellular Vesicles genetics
        Type: general
      – SubjectFull: Extracellular Vesicles metabolism
        Type: general
    Titles:
      – TitleFull: Cross-Species Identification of Urinary Small Extracellular Vesicle-Associated miR-223-3p as a Candidate Biomarker for Nephrolithiasis in a Discovery Cohort.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Chen BJ
      – PersonEntity:
          Name:
            NameFull: Uk JJ
      – PersonEntity:
          Name:
            NameFull: Shen CH
      – PersonEntity:
          Name:
            NameFull: Fang CY
      – PersonEntity:
          Name:
            NameFull: Lai YY
      – PersonEntity:
          Name:
            NameFull: Hong YW
      – PersonEntity:
          Name:
            NameFull: Eaw CY
      – PersonEntity:
          Name:
            NameFull: Chuang MC
      – PersonEntity:
          Name:
            NameFull: Chen JC
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 24
              M: 08
              Text: 2026 Aug 24
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1449-1907
          Numbering:
            – Type: volume
              Value: 23
            – Type: issue
              Value: 10
          Titles:
            – TitleFull: International journal of medical sciences
              Type: main
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