miR-486-3p Inhibiting BMP Signaling Pathway through Targeting on BMPR2 Increases the Risk of Ventricular Septal Defect

This study revealed that the expression of miR-486-3p was low during critical periods of early heart development, and it is found that the expression level was also low in human embryonic stem cells during the early stage of differentiation into cardiomyocytes. Yet, it is highly expressed in the heart tissue of the aborted fetus with VSD (ventricular septal defect) compared with the matched controls. In C57BL/6 mice, it is discovered that miR-486-3p was highly expressed in the myocardium and ventricular septum. The overexpression of miR-486-3p significantly inhibited cell proliferation, down-regulated the expression of epithelial cell markers, up-regulated the expression of mesenchymal cell markers and promoted cell migration. Forty-three candidate target genes were identified by bioinformatics and mouse models. The target gene BMPR2 was identified by qRT-PCR, Western blot and dual luciferase reporter assay. Finally, it is confirmed that miR-486-3p inhibited the activity of the BMP signaling pathway, and down-regulated the mRNA levels of the downstream target genes of the BMP signaling pathway. In summary, this research indicated that miR-486-3p might promote the occurrence of VSD by inhibiting BMP signaling pathway through targeting BMPR2. This research shed light on the future design of the possible therapeutic strategies of VSD.

CSTR: 32200.14.cjcb.2021.08.0006