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miR-322-5p targets IGF-1 and is suppressed in the heart of rats with pulmonary hypertension.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Connolly, Martin 
Garfield, Benjamin E 
Crosby, Alexi 
Morrell, Nick W 
Wort, Stephen J 

Abstract

Pulmonary arterial hypertension (PAH) is characterised by remodelling of the pulmonary vasculature leading to right ventricular hypertrophy. Here, we show that miR-322-5p (the rodent orthologue of miR-424-5p) expression is decreased in the right ventricle of monocrotaline-treated rats, a model of PAH, whereas a putative target insulin-like growth factor 1 (IGF-1) is increased. IGF-1 mRNA was enriched 16-fold in RNA immunoprecipitated with Ago2, indicating binding to miR-322-5p. In cell transfection experiments, miR-322-5p suppressed the activity of a luciferase reporter containing a section of the IGF-1 3' untranslated region (UTR) as well as IGF-1 mRNA and protein levels. Taken together, these data suggest that miR-322 targets IGF-1, a process downregulated in PAH-related RV hypertrophy.

Description

Keywords

IGF‐1, miR‐322/424, pulmonary arterial hypertension, right ventricular hypertrophy

Journal Title

FEBS Open Bio

Conference Name

Journal ISSN

2211-5463
2211-5463

Volume Title

8

Publisher

Wiley
Sponsorship
British Heart Foundation (None)
British Heart Foundation (None)