Large-scale microRNA functional high-throughput screening identifies miR-515-3p and miR-519e-3p as inducers of human cardiomyocyte proliferation

Renikunta HV, Lazarow K, Gong Y, Shukla PC, Nageswaran V, Giral H, Kratzer A, Opitz L, Engel F, Haghikia A, Costantino S, Paneni F, von Kries JP, Streckfuss-Bömeke K, Landmesser U, Jakob P (2023)

Publication Language: English

Publication Type: Journal article, Original article

Publication year: 2023

Journal

iScience Elsevier

Book Volume: 26

Article Number: 106593

Journal Issue: 5

DOI: 10.1016/j.isci.2023.106593

Open Access Link: https://www.sciencedirect.com/science/article/pii/S2589004223006703?via=ihub

Abstract

Ischemic cardiomyopathy, driven by loss of cardiomyocytes and inadequate proliferative response, persists to be a major global health problem. Using a functional high-throughput screening, we assessed differential proliferative potential of 2019 miRNAs after transient hypoxia by transfecting both miR-inhibitor and miR-mimic libraries in human iPSC-CM. Whereas miR-inhibitors failed to enhance EdU uptake, overexpression of 28 miRNAs substantially induced proliferative activity in hiPSC-CM, with an overrepresentation of miRNAs belonging to the primate-specific C19MC-cluster. Two of these miRNAs, miR-515-3p and miR-519e-3p, increased markers of early and late mitosis, indicative of cell division, and substantially alter signaling pathways relevant for cardiomyocyte proliferation in hiPSC-CM.

Authors with CRIS profile

Felix Engel Professur für Experimentelle Nieren- und Kreislaufforschung

Involved external institutions

Max Planck Institute for Heart and Lung Research / Max-Planck-Institut für Herz- und Lungenforschung DE Germany (DE) Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP) DE Germany (DE) Universitätsspital Zürich (USZ) CH Switzerland (CH) Deutsches Herzzentrum Berlin DE Germany (DE) University of Zurich / Universität Zürich (UZH) CH Switzerland (CH) Universitätsklinikum Göttingen DE Germany (DE)

How to cite

APA:

Renikunta, H.V., Lazarow, K., Gong, Y., Shukla, P.C., Nageswaran, V., Giral, H.,... Jakob, P. (2023). Large-scale microRNA functional high-throughput screening identifies miR-515-3p and miR-519e-3p as inducers of human cardiomyocyte proliferation. iScience, 26(5). https://doi.org/10.1016/j.isci.2023.106593

MLA:

Renikunta, Harsha V., et al. "Large-scale microRNA functional high-throughput screening identifies miR-515-3p and miR-519e-3p as inducers of human cardiomyocyte proliferation." iScience 26.5 (2023).

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