Circulating miR-145-5p and miR-133a-3p in pediatric sickle cell disease: biomarker potential for vaso-occlusive crises and disease activity.

Uložené v:
Podrobná bibliografia
Názov: Circulating miR-145-5p and miR-133a-3p in pediatric sickle cell disease: biomarker potential for vaso-occlusive crises and disease activity.
Autori: Fares R; Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Fayoum University, Fayoum, Egypt., Bakr S; Department of Clinical Pathology/Hematology, Faculty of Medicine, Fayoum University, P.O. Box: 63514, Fayoum, Egypt. salwabakr1@hotmail.com., El-Hamid RGA; Department of Pediatrics, Faculty of Medicine, Fayoum University, Fayoum, Egypt., Abdelaleem OO; Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Fayoum University, Fayoum, Egypt., Sharabi MM; Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Fayoum University, Fayoum, Egypt., Abdelwahed MY; Department of Physiology, Faculty of Medicine, Fayoum University, Fayoum, Egypt., Sherbieny H; Department of Medical Physiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt., Kamal M; Department of Clinical Pharmacy, Faculty of Pharmacy, Fayoum university, Fayoum, Egypt., Ali EY; Department of Clinical Pathology/Hematology, Faculty of Medicine, Fayoum University, P.O. Box: 63514, Fayoum, Egypt.
Zdroj: Annals of hematology [Ann Hematol] 2025 Nov; Vol. 104 (11), pp. 5625-5633. Date of Electronic Publication: 2025 Nov 07.
Spôsob vydávania: Journal Article
Jazyk: English
Informácie o časopise: Publisher: Springer Verlag Country of Publication: Germany NLM ID: 9107334 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0584 (Electronic) Linking ISSN: 09395555 NLM ISO Abbreviation: Ann Hematol Subsets: MEDLINE
Imprint Name(s): Publication: Berlin : Springer Verlag
Original Publication: Berlin ; New York : Springer International, c1991-
Výrazy zo slovníka MeSH: Anemia, Sickle Cell*/blood , Anemia, Sickle Cell*/genetics , Anemia, Sickle Cell*/complications , Anemia, Sickle Cell*/diagnosis , Anemia, Sickle Cell*/drug therapy , MicroRNAs*/blood, Humans ; Male ; Female ; Child ; Biomarkers/blood ; Case-Control Studies ; Adolescent ; Child, Preschool ; Hydroxyurea/therapeutic use ; Vaso-Occlusive Crises
Abstrakt: MicroRNAs (miRNAs) involving miR-145-5p and miR-133a-3p are increasingly recognized for their roles in modulating inflammation, oxidative stress, and vascular integrity, key processes implicated in sickle cell disease (SCD) pathophysiology. To investigate the expression levels of miR-145-5p and miR-133a-3p in pediatric SCD patients during vaso-occlusive crisis (VOC) as well as steady-state conditions, and to evaluate their potential as clinical biomarkers. A case-control study was conducted including 45 pediatric SCD patients (24 during VOC and 21 in steady-state) and 45 age- and sex-matched healthy controls. Plasma miR-145-5p and miR-133a-3p levels were quantified using real-time quantitative PCR and correlated with clinical characteristics, laboratory parameters, genotype, and hydroxyurea (HU) therapy. Circulating miR-133a-3p and miR-145-5p were significantly higher in SCD patients than in controls (p < 0.001), with a further elevation during VOC compared to steady-state (p < 0.050). While no significant association was found with genotype or HU therapy (p > 0.05), miR-133a-3p levels correlated significantly with fetal hemoglobin (HbF) (p = 0.006), reticulocyte count (p = 0.049), and urine albumin/creatinine ratio (p = 0.043). A strong positive correlation was observed between both miRNAs (r = 0.683, p < 0.001). Receiver Operating Characteristic (ROC) analysis demonstrated reasonable diagnostic accuracy of both miRNAs in distinguishing VOC from steady-state (AUC = 0.69). This study highlights the potential of miR-133a-3p and miR-145-5p as biomarkers for SCD activity. The association of miR-133a-3p with HbF and urine A/C ratio further suggests clinical relevance in vaso-occlusive complications. Larger longitudinal and functional studies are needed to validate these findings.
(© 2025. The Author(s).)
References: Biomed Pharmacother. 2018 Jul;103:851-857. (PMID: 29710501)
Cardiol J. 2022;29(2):284-292. (PMID: 32207842)
Bone Res. 2023 Jan 24;11(1):8. (PMID: 36690624)
Semin Cell Dev Biol. 2020 May;101:123-139. (PMID: 31879265)
Am J Hematol. 2010 Oct;85(10):746-51. (PMID: 20806231)
Exp Ther Med. 2021 Apr;21(4):373. (PMID: 33732346)
Hereditas. 2025 May 11;162(1):75. (PMID: 40350457)
Physiol Res. 2021 Mar 17;70(1):67-78. (PMID: 33453713)
J Natl Med Assoc. 1983 May;75(5):483-7. (PMID: 6864827)
Ann Transl Med. 2022 May;10(10):571. (PMID: 35722425)
Crit Care Med. 2014 May;42(5):1096-104. (PMID: 24413579)
PLoS One. 2022 Jan 6;17(1):e0262339. (PMID: 34990478)
Lancet. 2010 Dec 11;376(9757):2018-31. (PMID: 21131035)
Am J Transl Res. 2022 Jun 15;14(6):4251-4259. (PMID: 35836907)
Cell Death Dis. 2019 Sep 11;10(9):670. (PMID: 31511493)
J Int Med Res. 2019 Jul;47(7):3307-3319. (PMID: 31264490)
Eur J Pharmacol. 2023 Aug 15;953:175836. (PMID: 37329971)
Antioxidants (Basel). 2021 Oct 13;10(10):. (PMID: 34679742)
Int Immunopharmacol. 2020 Nov;88:106848. (PMID: 32771944)
Obes Facts. 2024;17(6):602-612. (PMID: 39236703)
Exp Anim. 2021 Aug 6;70(3):322-332. (PMID: 33658464)
Contributed Indexing: Keywords: Biomarker.; MiR-133a; MiR-145; MicroRNAs; Sickle cell disease; Vaso-occlusive crisis
Substance Nomenclature: 0 (MicroRNAs)
0 (MIRN133 microRNA, human)
0 (MIRN145 microRNA, human)
0 (Biomarkers)
X6Q56QN5QC (Hydroxyurea)
Entry Date(s): Date Created: 20251107 Date Completed: 20251202 Latest Revision: 20251205
Update Code: 20251205
PubMed Central ID: PMC12672820
DOI: 10.1007/s00277-025-06696-1
PMID: 41201586
Databáza: MEDLINE
Popis
Abstrakt:MicroRNAs (miRNAs) involving miR-145-5p and miR-133a-3p are increasingly recognized for their roles in modulating inflammation, oxidative stress, and vascular integrity, key processes implicated in sickle cell disease (SCD) pathophysiology. To investigate the expression levels of miR-145-5p and miR-133a-3p in pediatric SCD patients during vaso-occlusive crisis (VOC) as well as steady-state conditions, and to evaluate their potential as clinical biomarkers. A case-control study was conducted including 45 pediatric SCD patients (24 during VOC and 21 in steady-state) and 45 age- and sex-matched healthy controls. Plasma miR-145-5p and miR-133a-3p levels were quantified using real-time quantitative PCR and correlated with clinical characteristics, laboratory parameters, genotype, and hydroxyurea (HU) therapy. Circulating miR-133a-3p and miR-145-5p were significantly higher in SCD patients than in controls (p &lt; 0.001), with a further elevation during VOC compared to steady-state (p &lt; 0.050). While no significant association was found with genotype or HU therapy (p &gt; 0.05), miR-133a-3p levels correlated significantly with fetal hemoglobin (HbF) (p = 0.006), reticulocyte count (p = 0.049), and urine albumin/creatinine ratio (p = 0.043). A strong positive correlation was observed between both miRNAs (r = 0.683, p &lt; 0.001). Receiver Operating Characteristic (ROC) analysis demonstrated reasonable diagnostic accuracy of both miRNAs in distinguishing VOC from steady-state (AUC = 0.69). This study highlights the potential of miR-133a-3p and miR-145-5p as biomarkers for SCD activity. The association of miR-133a-3p with HbF and urine A/C ratio further suggests clinical relevance in vaso-occlusive complications. Larger longitudinal and functional studies are needed to validate these findings.<br /> (© 2025. The Author(s).)
ISSN:1432-0584
DOI:10.1007/s00277-025-06696-1