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Development. 2013 May;140(10):2172-80. doi: 10.1242/dev.084475. Epub 2013 Apr 11.

miR-21 represses Pdcd4 during cardiac valvulogenesis.

Author information

1
Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.

Abstract

The discovery of small non-coding microRNAs has revealed novel mechanisms of post-translational regulation of gene expression, the implications of which are still incompletely understood. We focused on microRNA 21 (miR-21), which is expressed in cardiac valve endothelium during development, in order to better understand its mechanistic role in cardiac valve development. Using a combination of in vivo gene knockdown in zebrafish and in vitro assays in human cells, we show that miR-21 is necessary for proper development of the atrioventricular valve (AV). We identify pdcd4b as a relevant in vivo target of miR-21 and show that protection of pdcd4b from miR-21 binding results in failure of AV development. In vitro experiments using human pulmonic valve endothelial cells demonstrate that miR-21 overexpression augments endothelial cell migration. PDCD4 knockdown alone was sufficient to enhance endothelial cell migration. These results demonstrate that miR-21 plays a necessary role in cardiac valvulogenesis, in large part due to an obligatory downregulation of PDCD4.

PMID:
23578931
PMCID:
PMC3640220
DOI:
10.1242/dev.084475
[Indexed for MEDLINE]
Free PMC Article

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