Oncotarget

Research Papers:

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

Xiang Ling, Dongbo Yao, Lumei Kang, Jing Zhou, Ying Zhou, Hui Dong, Keping Zhang, Lei Zhang and Hongping Chen _

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Oncotarget. 2017; 8:84403-84416. https://doi.org/10.18632/oncotarget.21218

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Abstract

Xiang Ling1,*, Dongbo Yao2,*, Lumei Kang3,*, Jing Zhou1, Ying Zhou1, Hui Dong1, Keping Zhang4, Lei Zhang1 and Hongping Chen2,5

1Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China

2Department of Histology and Embryology, Medical College, Nanchang University, Nanchang, Jiangxi 330006, China

3Department of Animal Science, Medical College, Nanchang University, Nanchang, Jiangxi 330006, China

4Department of Experimental Teaching, Medical College, Nanchang University, Nanchang, Jiangxi 330006, China

5Jiangxi Province Key Laboratory of Tumor Pathogen’s and Molecular Pathology, Nanchang, Jiangxi 330006, China

*These authors have contributed equally to this work

Correspondence to:

Hongping Chen, email: [email protected]

Keywords: miR-155-3p, myogenic enhance factor 2C, embryonic stem cell, cardiomyocyte, extracellular signal-regulate kinase

Received: August 24, 2017     Accepted: August 27, 2017     Published: September 23, 2017

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.


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