MicroRNA-223-3p is a determinant of platelet procoagulant activity

Article Article scientifique Article MicroRNA-223-3p is a determinant of platelet procoagulant activity eng 2025-10-07 2026-01-13 author Charlon Julia France 0009-0001-8858-6311 Faculty of Medicine, University of Geneva, Geneve, Switzerland. 960900 author Nolli Severine Faculty of Medicine and University Hospitals of Geneva, Geneva, Switzerland. 591816 Département de médecine (DEMED) author Geindre Sylvie Françoise Faculty of Medicine, University of Geneva, Genève, Switzerland. 133391 author Ciepla Paulina 0000-0002-5139-9635 Faculty of Medicine, University of Geneva, Geneve, Switzerland. 961001 author Reny Jean-Luc 0000-0002-7528-7363 Division of General Internal Medicine, Geneva University Hospitals, Geneve, Switzerland. 704339 Département de médecine (DEMED) author Fontana Pierre 0000-0003-1546-0774 Division of Angiology and Hemostasis, Geneva University Hospitals, Geneve, Switzerland. 135328 Département de médecine (DEMED) 83-94 10.1182/bloodadvances.2024015290 41056510 2473-9529 PMC12804390 https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2024015290/547626/MicroRNA-223-3p-is-a-determinant-of-platelet MicroRNAs (miRNAs) are regulators of platelet function and may thus contribute to inter-individual variability in platelet reactivity. MiR-223-3p is the most abundant of the platelet-derived miRNAs. Several studies have reported an association between miR-223-3p levels and platelet reactivity or the recurrence of cardiovascular events, but this miRNA's impact on platelet function is still poorly understood. We aimed to investigate miR-223-3p's effects on platelet reactivity in platelets derived from human hematopoietic stem cells (CD34+) and to study the underlying mechanisms of its action. MiR-223-3p upregulation and downregulation were carried out by transfecting megakaryocytes (MKs) derived from CD34+ cells with a miR-223-3p mimic or Cas9/sgRNAs ribonucleoprotein complexes, respectively. Flow cytometry was used to quantify the expression of surface markers of MKs and platelets, platelet production, and platelet reactivity. Platelet-supported thrombin generation was quantified in human plasma. Downregulation of miR-223-3p resulted in fewer proplatelet swellings and decreased platelet production. MiR-223-3p upregulation and downregulation affected the proportion of procoagulant platelets. This phenotype was mirrored by changes in the gene expression of the transmembrane protein 16F (TMEM16F), a phospholipid scramblase that plays a key role in the generation of procoagulant platelets. A luciferase reporter gene assay validated that TMEM16F mRNA was a direct target of miR-223-3p. Platelet-supported thrombin generation was reduced when miR-223-3p was upregulated. In conclusion, miR-223-3p modulates the generation of procoagulant platelets. Blood Coagulation / genetics Blood Platelets / cytology Blood Platelets / metabolism Gene Expression Regulation Humans Megakaryocytes / cytology Megakaryocytes / metabolism MicroRNAs / genetics Platelet Activation / genetics Thrombin / metabolism Dewey 616 Swiss National Science Foundation Role of microRNAs in platelet-mediated thrombus formation: towards a personalized antithrombotic strategy in cardiovascular patients 196864 CH 56 Département de médecine 221 false 11 Plaquettes et antithrombotiques 13 319 Groupe Perrier Arnaud (Médecine interne générale, de réhabilitation et de gériatrie) 585 Blood advances 10 1 3ab2d231-bcfd-4897-bfd6-3239f7c29b33 Article (Published version) Public blooda_adv-2024-015290-main.pdf 1245668 application/pdf CC BY-NC-ND-4.0 7356a5537f6d1b832541104e8cf29c288819edb3d178ee43d26f2436abdad24c fc3b1c78-661d-4cda-b904-94445e9c8788 Supplemental data Public blooda_adv-2024-015290-mmc1.pdf 1729495 application/pdf 8085059feaf09bbff465c8b00786c2b3cfb787a2036946dcb53f80ee5745ca6b Vignette Public blooda_adv-2024-015290-ga1.jpeg 242072 image/png openAccess Faculté de médecine / Section de médecine clinique / Département de médecine

Title	Published in	Access level	OA Policy	Year	Views	Downloads

MicroRNA-223-3p is a determinant of platelet procoagulant activity	Blood advances			2026	26	177

Archive ouverte UNIGE

Ciepla, Paulina