VPB0374 - The role of miRNAs in regulation of platelet activity - a bioinformatic analysis

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

Zofia Wicik, PhD

Senior Researcher
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland
Warsaw, Mazowieckie, Poland

Co-Author(s)

CE

Ceren Eyileten

Senior Researcher
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland
Warsaw, Mazowieckie, Poland
DJ

Daniel Jakubik

PhD candidate
Medical University of Warsaw
Warsaw, Mazowieckie, Poland
JJ

Joanna Jarosz-Popek

PhD candidate
Medical University of Warsaw
Warsaw, Mazowieckie, Poland
MW

Marta Wolska

PhD candidate
Medical University of Warsaw
warsaw, Mazowieckie, Poland
AN

Anna Nowak

PhD candidate
Medical University of Warsaw
Warsaw, Mazowieckie, Poland
DK

Disha Keshwani

Student
1. Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland
Warsaw, Mazowieckie, Poland
DV

Dirk Von Lewinski

Prof
Medical University of Graz
Graz, Steiermark, Austria
HS

Harald Sourij

Prof
Medical University of Graz
Graz, Steiermark, Austria
JS

Jolanta M. Siller-Matula

Professor
Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna,1090 Vienna, Austria
Vienna, Wien, Austria
MP

Marek Postula

Prof
Medical University of Warsaw
Warsaw, Mazowieckie, Poland

Background: Circulating miRNAs can be determined from plasma, serum, or whole blood, and they can be used as diagnostic and prognostic biomarkers as well as therapeutic targets including cardiovascular diseases (CVDs).

Aims: Herein, we present original results from bioinformatic analyses, which identified top 22 platelet-related miRNAs including hsa-miR-320a, hsa-miR-16-5p, hsa-miR-106a-5p, hsa-miR-320b, hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-92a-3p as widely involved in platelet reactivity and associated diseases, including CVDs, Alzheimer’s and cerebrovascular diseases, cancer, hypertension.

Methods: Bioinformatics analysis miRNA targets prediction, data filtering, and visualization as interaction networks, Identification of the top miRNAs regulating genes associated with platelet-related processes and expressed in relevant tissues, Identification of the most promising genes targeted by platelet-related miRNAs, Enrichment analysis by in silico analysis

Results: Analysis focused on the identification of the highly regulatory targets shared between those miRNAs identified 43 of them. Best ranked genes associated with overall platelet activity and most susceptible for noncoding regulation were PTEN, PIK3R1, CREB1, APP and MAPK1. Top targets also strongly associated with CVD were VEGFA, IGF1, ESR1, BDNF and PPARG. Top targets associated also with other platelet-related diseases including cancer identified in our study were TP53, KRAS (highest number of hits overall) and CCND1. The most affected pathways by top miRNAs and top targets included diseases associated with GFRs, platelet activation, signaling and aggregation, Signaling by VEGF, MAPK family signaling cascades and signaling by Interleukins. Terms specific only for miRNAs included coronary artery disease, platelet degranulation and neutrophil degranulation, while for targeted genes it was ESR1 mediated signaling, extra-nuclear estrogen signaling and endometriosis.

Conclusion(s): Our results show the novel features of platelet physiology and may provide a basis for further clinical studies focused on platelet reactivity. They also show in which aspects miRNAs can be promising biomarkers of platelet related pathological processes.