MiR-184 directly targets Wnt3 in cardiac mesoderm differentiation of embryonic stem cells

Abstract

Embryonic stem (ES) cells have the property of self-renewal and multi-directional differentiation, and provide an ideal model for studying early embryo development in vitro. Wnt3, as Wnt family member 3, plays a vital role during ES cell differentiation. However, the exact regulatory mechanism of Wnt3 remains to be elucidated. MicroRNAs can directly regulate gene expression at the post-transcriptional level and play critical function in cell fate determination. Here, we found the expression level of miR-184 decreased when ES cells differentiated into cardiac mesoderm then increased during the process as differentiated into cardiomyocytes, which negatively correlated with the expression of Wnt3. Overexpression of miR-184 during the process of ES cell differentiation into cardiac mesoderm repressed cardiac mesoderm differentiation and cardiomyocyte formation. Bioinformatics prediction and mechanism studies showed that miR-184 directly bound to the 3′UTR region of Wnt3 and inhibited the expression level of Wnt3. Consistently, knockdown of Wnt3 mimicked the effects of miR-184-overexpression on ES cell differentiation into cardiac mesoderm, whereas overexpression of Wnt3 rescued the inhibition effects of miR-184 overexpression on ES cell differentiation. These findings demonstrated that miR-184 is a direct regulator of Wnt3 during the differentiation process of ES cells, further enriched the epigenetic regulatory network of ES cell differentiation into cardiac mesoderm and cardiomyocytes.

Clinical and genetic associations of asymmetric apical and septal left ventricular hypertrophy

“…For global LVM, seventeen independent variants reached genomewide significance (Table 1), including many genes previously recognized to be associated with cardiovascular disease. BAG3, BTN3A2 and other identified variants include those previously associated with hypertrophic cardiomyopathy, restrictive cardiomyopathy, mitral valve disease, and left ventricular dilation [16][17][18][19][20][21][22][23][24][25] . GWAS of septal mass identified three unique genes (HIVEP3, ESYT3, and HMGA1) and nine genes shared with LVM.…”

microRNA-184 in the landscape of human malignancies: a review to roles and clinical significance

“…In the fly Drosophila, miR-184 is found with involvement in numerous biological functions, particularly female germline stem cell differentiation [36]. It is also documented with crucial roles regulating the differentiation of other types of stem cells like embryonic stem (ES) cells and periodontal ligament stem cells as well as physiological functions of granulosa cells [37][38][39]. Particularly, its function in the regulation of cell physiologic processes like neural cells' growth and differentiation may suggest therapeutic potential in human diseases [40].…”

“…miR-184, as a brain-specific miRNA, is discovered to exert pathogenic roles in Rett syndrome [59], which the disease is characterized by neuropsychiatric abnormalities [60]. miR-184 plays a substantial role in differentiating ES cells to some cardiac cells like mesoderm and cardiomyocytes by regulating Wnt3 expression [37]. The results of a cell model study have shown that inhibition of miR-184 suppressed inflammation and oxidative stress process, and as a result prevented apoptosis in cardiomyocytes [61].…”

The miR‐184‐3p promotes rice black‐streaked dwarf virus infection by suppressing Ken in Laodelphax striatellus (Fallén)

“…[4][5][6][7][8] It plays a critical role in development, cell proliferation, differentiation, oxidative modification, and regulation of cell apoptosis. [9][10][11][12] The microRNA-184 responds to and regulates animal viral infection in host cells. The expression of miR-184-3p increased after reticuloendotheliosis virus and avian leukosis virus infection in both exosomes and chick embryo fibroblast (CEF) cells.…”

“…MicroRNA‐184 is a conserved miRNA with high abundance in different species 4–8 . It plays a critical role in development, cell proliferation, differentiation, oxidative modification, and regulation of cell apoptosis 9–12 . The microRNA‐184 responds to and regulates animal viral infection in host cells.…”