MiR‐148a promotes myocardial differentiation of human bone mesenchymal stromal cells via DNA methyltransferase 1 (DNMT1)

Abstract

MicroRNAs have potential to modulate the differentiation of stem cells. In previous study, we found that miR-148a was up-regulated in myocardial differentiation of human bone mesenchymal stromal cells (hBMSCs) induced by 5'-azacytidine. However, the role of miR-148a in regulating this process still remains unclear. In this study, we investigated the function and molecular mechanism of miR-148a in myocardial differentiation of hBMSCs. We found that miR-148a was significantly increased while DNA methyltransferase 1 (DNMT1) was significantly decreased in myocardial differentiation of hBMSCs. Then, the dual luciferase reporter assays method indicated that DNMT1 was the direct target of miR-148a. In addition, we showed that up-regulation of miR-148a could enhance myocardial differentiation of hBMSCs, while down-regulation of miR-148a could inhibit myocardial differentiation process. Moreover, knockdown of DNMT1 could block the role of miR-148a in promoting myocardial differentiation of hBMSCs. Finally, MiR-148a acted on methylation level of GATA-4 and knockdown of DNMT1 could block this function. Therefore, our results indicate that miR-148a plays a vital role in regulating myocardial differentiation of hBMSCs by targeting DNMT1.