Involment of RAS/ERK1/2 signaling and MEF2C in miR-155-3p inhibition-triggered cardiomyocyte differentiation of embryonic stem cell

Abstract

MicroRNAs (miRNAs) are short, noncoding RNAs that regulate post-transcriptional gene expression by targeting messenger RNAs (mRNAs) for cleavage or translational repression. Growing evidence indicates that miR-155 expression changes with the development of heart and plays an important role in heart physiopathology. However, the role of miR-155 in cardiac cells differentiation is unclear. Using the well-established embryonic stem cell (ESC), we demonstrated that miR-155-3p expression was down-regulated during cardiogenesis from mouse ESC. By contrast, the myogenic enhance factor 2C (MEF2C), a predicted target gene of miR-155-3p, was up-regulated. We further demonstrated that miR-155-3p inhibition increased the percentage of embryoid bodies (EB) beating and up-regulated the expression of cardiac specific markers, GATA4, Nkx2.5, and cTnT mRNA and protein. Notably, miR- 155-3p inhibition caused upregulation of MEF2C, KRAS and ERK1/2. ERK1/2 inhibitor, PD98059 significantly decreased the expression of MEF2C protein. These findings indicate that miR-155-3p inhibition promotes cardiogenesis, and its mechanisms are involved in the RAS-ERK1/2 signaling and MEF2C.