In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2016-02-10)
Abstract:
MiRNA 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.
Type of Medium:
Online Resource
ISSN:
2045-2322
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2016
detail.hit.zdb_id:
2615211-3
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