Identification of circulating miRNA alterations in diabetes patients excluding periodontitis effects: insights into target gene downregulation in diabetic complications.
Uloženo v:
| Název: | Identification of circulating miRNA alterations in diabetes patients excluding periodontitis effects: insights into target gene downregulation in diabetic complications. |
|---|---|
| Autoři: | Lee HS; Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Republic of Korea., Yu Y; Medical Research Institute, Pusan National University, Yangsan, Republic of Korea., Kim HJ; Department of Periodontology, Dental and Life Science Institute, Pusan National University, School of Dentistry, Yangsan, Republic of Korea.; Periodontal Disease Signaling Network Research Center, School of Dentistry, Pusan National University, Yangsan, Republic of Korea.; Department of Periodontics and Dental Research Institute, Pusan National University Dental Hospital, Yangsan, Republic of Korea., Oh JM; Periodontal Disease Signaling Network Research Center, School of Dentistry, Pusan National University, Yangsan, Republic of Korea.; Department of Oral Biochemistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea.; Institute for Future Earth, Pusan National University, Busan, Republic of Korea., Park HR; Periodontal Disease Signaling Network Research Center, School of Dentistry, Pusan National University, Yangsan, Republic of Korea.; Department of Oral Pathology, Dental & Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea.; Department of Periodontology and Dental Research Institute, Pusan National University Dental Hospital, Yangsan, Republic of Korea., Kim YH; Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Republic of Korea.; Periodontal Disease Signaling Network Research Center, School of Dentistry, Pusan National University, Yangsan, Republic of Korea.; Department of Biomedical Informatics, School of Medicine, Pusan National University, Yangsan, Republic of Korea.; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea. |
| Zdroj: | Annals of medicine [Ann Med] 2025 Dec; Vol. 57 (1), pp. 2567609. Date of Electronic Publication: 2025 Nov 10. |
| Způsob vydávání: | Journal Article |
| Jazyk: | English |
| Informace o časopise: | Publisher: Informa Healthcare Country of Publication: England NLM ID: 8906388 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2060 (Electronic) Linking ISSN: 07853890 NLM ISO Abbreviation: Ann Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: London : Informa Healthcare Original Publication: Helsinki : Finnish Medical Society Duodecim, 1989- |
| Výrazy ze slovníku MeSH: | Circulating MicroRNA*/blood , Circulating MicroRNA*/genetics , Diabetes Complications*/genetics , Diabetes Complications*/blood , Diabetes Mellitus, Type 2*/genetics , Diabetes Mellitus, Type 2*/complications , Diabetes Mellitus, Type 2*/blood , MicroRNAs*/blood , MicroRNAs*/genetics, Humans ; Down-Regulation ; Male ; Middle Aged ; Female ; Exosomes/metabolism ; Exosomes/genetics ; Gene Expression Profiling ; Aged ; Periodontitis/genetics ; Sequence Analysis, RNA ; Gene Expression Regulation |
| Abstrakt: | Background: Diabetes mellitus (DM) induces systemic complications through chronic metabolic dysregulation. Circulating exosomal microRNAs (miRNAs) are emerging as key regulators of post-transcriptional gene expression and may drive diabetes-associated pathologies. Although miRNAs have been widely studied in diabetes, the characterization of PD-independent miRNA signatures across tissues remains limited. This study aimed to identify DM-specific miRNA alterations and their contribution to systemic metabolic dysfunction independent of PD. Methods: Exosomes were isolated from plasma samples, and small RNA sequencing was performed to identify differentially expressed miRNAs (DE-miRs) using the limma R package. Predicted target genes were identified using TargetScan and validated through bulk RNA sequencing datasets from four tissues-foot, kidney, pancreas, and retina. Differentially expressed genes (DEGs) were analyzed, followed by Gene Ontology Biological Process (GOBP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment to elucidate diabetes-related mechanisms. Results: We identified 9 upregulated and 6 downregulated DE-miRs specific to the diabetic group. TargetScan predicted 216 upregulated and 64 downregulated target genes. Functional validation revealed that these genes were enriched in pathways related to glucose metabolism, cellular stress response, and tissue repair. Notably, SREK1 and GLIPR1 were commonly detected across all four tissues, suggesting potential systemic regulators of diabetes-related complications. Conclusion: This study suggests that circulating exosomal miRNAs, independent of periodontitis, may function as systemic regulators in diabetes. Unlike previous studies, which did not distinguish co-morbid periodontitis, we specifically defined PD-independent miRNA signatures and validated their cross-organ regulatory effects on target genes. Our results revealed a cross-organ miRNA-mRNA regulatory network and identified common regulatory targets. These findings provide insights into both systemic and organ-specific mechanisms underlying diabetic complications and highlight the potential of miRNAs as biomarkers and therapeutic targets. |
| References: | Front Physiol. 2021 Oct 27;12:709438. (PMID: 34776994) Gastroenterology. 2012 Jun;142(7):1571-1580.e6. (PMID: 22374165) FEBS Lett. 2009 Dec 3;583(23):3770-83. (PMID: 19887069) Periodontol 2000. 2007;43:233-44. (PMID: 17214841) Glia. 2012 Dec;60(12):2050-64. (PMID: 23002008) Diabetes Metab Syndr Obes. 2021 Aug 10;14:3567-3602. (PMID: 34413662) Cell. 2016 Jan 14;164(1-2):141-155. (PMID: 26774822) J Clin Invest. 2023 Feb 15;133(4):. (PMID: 36656641) Int J Chron Obstruct Pulmon Dis. 2021 Oct 08;16:2817-2832. (PMID: 34675506) J Clin Invest. 2025 Jun 22;135(16):. (PMID: 40549565) Cureus. 2023 Sep 20;15(9):e45615. (PMID: 37868469) Elife. 2021 Oct 26;10:. (PMID: 34698632) Cold Spring Harb Perspect Biol. 2010 May;2(5):a001875. (PMID: 20452960) J Manag Care Spec Pharm. 2018 Sep;24(9-a Suppl):S5-S13. (PMID: 30156443) Lancet. 2009 May 23;373(9677):1743-4. (PMID: 19465216) Leukemia. 2022 Apr;36(4):956-969. (PMID: 35110726) World J Diabetes. 2022 Dec 15;13(12):1106-1121. (PMID: 36578865) Front Pediatr. 2022 Jun 22;10:919996. (PMID: 35813387) Int J Mol Sci. 2024 Dec 09;25(23):. (PMID: 39684917) Genes Dev. 2013 May 1;27(9):1059-71. (PMID: 23651858) Indian J Med Res. 2014 Nov;140(5):579-81. (PMID: 25579136) Mol Cell. 2012 Dec 28;48(6):875-87. (PMID: 23142081) J Neurosci. 2014 Jun 18;34(25):8630-45. (PMID: 24948817) EPMA J. 2023 Feb 13;14(1):21-42. (PMID: 36866156) J Cell Physiol. 2016 Jan;231(1):25-30. (PMID: 26031493) Nucleic Acids Res. 2015 Apr 20;43(7):e47. (PMID: 25605792) Arterioscler Thromb Vasc Biol. 2018 Jan;38(1):19-25. (PMID: 29191923) Signal Transduct Target Ther. 2021 Nov 10;6(1):383. (PMID: 34753929) J Diabetes Res. 2022 May 13;2022:4629419. (PMID: 35601016) Nat Commun. 2022 Mar 16;13(1):1363. (PMID: 35296659) Transl Oncol. 2009 Aug 18;2(3):107-16. (PMID: 19701494) Cancer Gene Ther. 2022 Nov;29(11):1720-1730. (PMID: 35760898) Front Cell Neurosci. 2023 Dec 14;17:1289966. (PMID: 38161998) Diabetologia. 2012 Jan;55(1):21-31. (PMID: 22057194) Nat Commun. 2020 Nov 23;11(1):5938. (PMID: 33230096) Diabetes Res Clin Pract. 2022 Jan;183:109119. (PMID: 34879977) World J Diabetes. 2023 Mar 15;14(3):130-146. (PMID: 37035220) Int J Cancer. 2014 Apr 15;134(8):2003-13. (PMID: 24590455) J Biol Chem. 2022 Mar;298(3):101685. (PMID: 35131264) J Extracell Vesicles. 2018 Nov 23;7(1):1535750. (PMID: 30637094) Diabetes Care. 2023 Jan 1;46(1):209-221. (PMID: 36548709) Sci Rep. 2023 Aug 28;13(1):14078. (PMID: 37640779) Int J Mol Sci. 2020 Dec 04;21(23):. (PMID: 33291683) Mol Cell Biol. 2009 May;29(10):2804-15. (PMID: 19273596) Anal Chem. 2014 Sep 16;86(18):9343-9. (PMID: 25191694) Theranostics. 2015 Jul 13;5(10):1122-43. (PMID: 26199650) World J Diabetes. 2024 May 15;15(5):797-809. (PMID: 38766426) Physiol Rev. 2013 Jan;93(1):137-88. (PMID: 23303908) Elife. 2015 Aug 12;4:. (PMID: 26267216) Cardiovasc Res. 2014 Feb 1;101(2):326-34. (PMID: 24296650) |
| Contributed Indexing: | Keywords: Diabetes mellitus; Pancreatic dysfunction; circulating exosomal microRNAs; diabetic foot ulcer; diabetic nephropathy; diabetic retinopathy; miRNA biomarkers; periodontitis; periodontitis with diabetes mellitus (PDDM) |
| Substance Nomenclature: | 0 (Circulating MicroRNA) 0 (MicroRNAs) |
| Entry Date(s): | Date Created: 20251110 Date Completed: 20251112 Latest Revision: 20251113 |
| Update Code: | 20251113 |
| PubMed Central ID: | PMC12604137 |
| DOI: | 10.1080/07853890.2025.2567609 |
| PMID: | 41208460 |
| Databáze: | MEDLINE |
Full Text 
Full Text Finder 
Nájsť tento článok vo Web of Science | Abstrakt: | Background: Diabetes mellitus (DM) induces systemic complications through chronic metabolic dysregulation. Circulating exosomal microRNAs (miRNAs) are emerging as key regulators of post-transcriptional gene expression and may drive diabetes-associated pathologies. Although miRNAs have been widely studied in diabetes, the characterization of PD-independent miRNA signatures across tissues remains limited. This study aimed to identify DM-specific miRNA alterations and their contribution to systemic metabolic dysfunction independent of PD.<br />Methods: Exosomes were isolated from plasma samples, and small RNA sequencing was performed to identify differentially expressed miRNAs (DE-miRs) using the limma R package. Predicted target genes were identified using TargetScan and validated through bulk RNA sequencing datasets from four tissues-foot, kidney, pancreas, and retina. Differentially expressed genes (DEGs) were analyzed, followed by Gene Ontology Biological Process (GOBP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment to elucidate diabetes-related mechanisms.<br />Results: We identified 9 upregulated and 6 downregulated DE-miRs specific to the diabetic group. TargetScan predicted 216 upregulated and 64 downregulated target genes. Functional validation revealed that these genes were enriched in pathways related to glucose metabolism, cellular stress response, and tissue repair. Notably, SREK1 and GLIPR1 were commonly detected across all four tissues, suggesting potential systemic regulators of diabetes-related complications.<br />Conclusion: This study suggests that circulating exosomal miRNAs, independent of periodontitis, may function as systemic regulators in diabetes. Unlike previous studies, which did not distinguish co-morbid periodontitis, we specifically defined PD-independent miRNA signatures and validated their cross-organ regulatory effects on target genes. Our results revealed a cross-organ miRNA-mRNA regulatory network and identified common regulatory targets. These findings provide insights into both systemic and organ-specific mechanisms underlying diabetic complications and highlight the potential of miRNAs as biomarkers and therapeutic targets. |
|---|---|
| ISSN: | 1365-2060 |
| DOI: | 10.1080/07853890.2025.2567609 |