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  • 1. Jafarzadeh, Meisam
    et al.
    Soltani, Bahram Mohammad
    Ekhteraei-Tousi, Samaneh
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Behmanesh, Mehrdad
    Hsa-miR-497 as a new regulator in TGF beta signaling pathway and cardiac differentiation process2018In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 675, p. 150-156Article in journal (Refereed)
    Abstract [en]

    Cardiosphere-derived cells (CDCs) contain cardiac stem cell subpopulations and are introduced as useful source for cardiac differentiation and therapy. Furthermore, research has highlighted miRNAs important role in various biological processes and cardiogenesis. Here, we intended to investigate the effect of hsa-miR-497 (miR-497) on TGF beta signaling pathway genes expression during the process of CDCs differentiation to cardiomyocytes. CDCs were successfully differentiated to the cardiac-like cells. In this study, we found that after cardiac differentiation induction, miR-497 expression was significantly decreased. Computational miRNA target prediction analyses revealed that TGF beta signaling pathway is a possible target of miR-497. Therefore, miR-497 was overexpressed in CDCs before the induction of differentiation. TGF beta 1, TGF beta R1, TGF beta R2, and SMAD3 genes expression level was decreased after miR-497 overexpression. Also, immunocytochemistry and cell morphology analysis indicated that miR-497 overexpression affecting cardiac differentiation process. Finally, direct interaction of miR-497 with 3'-UTR sequence of TGF beta R1 was supported through dual luciferase assay, consistent with miR-497 reported negative effect on SMAD3 expression. Accordingly, here a model of miR-497 involvement in regulation of TGF beta signaling pathway is introduced in which, side branches of TGF beta signaling pathway downregulate miR-497 to ensure upregulation of TGF beta R1 and TGF beta R2 and finally stronger TGF beta signaling.

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