Author:
Wang Yongshun,Liu Jingjin,Cui Jinjin,Sun Meng,Du Wenjuan,Chen Tao,Ming Xing,Zhang Lulu,Tian Jiangtian,Li Ji,Yin Li,Liu Fang,Pu Zhongyue,Lv Bo,Hou Jingbo,Yu Bo
Abstract
AbstractMiRNA expression was determined in both proliferating and differentiated cardiac
stem cells (CSCs) through a comprehensive miRNA microarray analysis. We selected
miR218 for functional follow-up studies to examine its significance in CSCs. First,
we observed that the expression of miR218 was altered in CSCs during differentiation
into cardiomyocytes and transfection of an miR218 mimic or miR218 inhibitor affected
the myocardial differentiation of CSCs. Furthermore, we observed that a negative
regulator of Wnt signaling, sFRP2, was a direct target of miR218 and the protein
levels of sFRP2 were increased in cells transfected with the synthetic miR218
inhibitor. In contrast, transfection with the miR218 mimic decreased the expression
of sFRP2 and potentiated Wnt signaling. The subsequent down-regulation of sFRP2 by
shRNA potentiated Wnt signaling, contributing to a gene expression program that is
important for CSC proliferation and cardiac differentiation. Specifically, canonical
Wnt signaling induced miR218 transcription. Thus, miR218 and Wnt signaling were
coupled through a feed-forward positive feedback loop, forming a biological
regulatory circuit. Together, these results provide the first evidence that miR218
plays an important role in CSC proliferation and differentiation through the
canonical Wnt signaling pathway.
Publisher
Springer Science and Business Media LLC
Cited by
22 articles.
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