Open AccessmiR‐322‐5p targets IGF ‐1 and is suppressed in the heart of rats with pulmonary hypertension
Author(s) -
Connolly Martin,
Garfield Benjamin E.,
Crosby Alexi,
Morrell Nick W.,
Wort Stephen J.,
Kemp Paul R.
Publication year - 2018
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12369
Subject(s) - untranslated region , three prime untranslated region , messenger rna , luciferase , ventricle , endocrinology , pulmonary hypertension , medicine , microrna , downregulation and upregulation , transfection , right ventricular hypertrophy , muscle hypertrophy , biology , chemistry , gene , biochemistry
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.