miR-322-5p targets IGF-1 and is suppressed in the heart of rats with pulmonary hypertension
File(s)Connolly_et_al-2018-FEBS_Open_Bio.pdf (409.57 KB)
Published version
Author(s)
Type
Journal Article
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.
Date Issued
2017-12-18
Date Acceptance
2017-12-11
Citation
FEBS Open Bio, 2017, 8 (3), pp.339-348
ISSN
2211-5463
Publisher
Elsevier
Start Page
339
End Page
348
Journal / Book Title
FEBS Open Bio
Volume
8
Issue
3
Copyright Statement
FEBS Open Bio (2017) © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Medical Research Council (MRC)
British Heart Foundation
Grant Number
MR/K023918/1
FS/14/71/31038
Subjects
IGF‐1
miR‐322/424
pulmonary arterial hypertension
right ventricular hypertrophy
Publication Status
Published