New tricks with old dogs

• Verfasst von: Bencun, Maja [VerfasserIn]
• Verfasst von: Britto-Borges, Thiago [VerfasserIn]
• Verfasst von: Eschenbach, Jessica [VerfasserIn]
• Verfasst von: Dieterich, Christoph [VerfasserIn]
• Titel: New tricks with old dogs
• Titelzusatz: computational identification and experimental validation of new miRNA-mRNA regulation in hiPSC-CMs
• Verf.angabe: Maja Bencun, Thiago Britto-Borges, Jessica Eschenbach and Christoph Dieterich
• E-Jahr: 2022
• Jahr: 6 February 2022
• Umfang: 17 S.
• Fussnoten: Published: 6 February 2022 ; Gesehen am 13.06.2022
• Titel Quelle: Enthalten in: Biomedicines
• Ort Quelle: Basel : MDPI, 2013
• Jahr Quelle: 2022
• Band/Heft Quelle: 10(2022), 2, Artikel-ID 391, Seite 1-17
• ISSN Quelle: 2227-9059
• DOI: doi:10.3390/biomedicines10020391
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: beta-adrenergic stress
• Sach-SW: cardiac differentiation
• Sach-SW: cardiomyocyte
• Sach-SW: cardiovascular biology
• Sach-SW: miRNA
• Sach-SW: miRNA-mRNA interaction
• Sach-SW: stem cell
• Sach-SW: target prediction
• K10plus-PPN: 1806877392

Abstract

Cardiovascular disease is still the leading cause of morbidity and mortality worldwide. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have become a valuable widespread in vitro model to study cardiac disease. Herein, we employ the hiPSC-CM model to identify novel miRNA-mRNA interaction partners during cardiac differentiation and β-adrenergic stress. Whole transcriptome and small RNA sequencing data were combined to identify novel miRNA-mRNA interactions. Briefly, mRNA and miRNA expression profiles were integrated with miRNA target predictions to identify significant statistical dependencies between a miRNA and its candidate target set. We show by experimental validation that our approach discriminates true from false miRNA target predictions. Thereby, we identified several differentially expressed miRNAs and focused on the two top candidates: miR-99a-5p in the context of cardiac differentiation and miR-212-3p in the context of β-adrenergic stress. We validated some target mRNA candidates by 3′UTR luciferase assays as well as in transfection experiments in the hiPSC-CM model system. Our data show that iPSC-derived cardiomyocytes and computational modeling can be used to uncover new valid miRNA-mRNA interactions beyond current knowledge.