MiR-150 Attenuates Maladaptive Cardiac Remodeling Mediated by Long Noncoding RNA MIAT and Directly Represses Profibrotic
RNA, untranslated
carvedilol
fibroblasts
microRNAs
transcriptome
Journal
Circulation. Heart failure
ISSN: 1941-3297
Titre abrégé: Circ Heart Fail
Pays: United States
ID NLM: 101479941
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
pubmed:
11
1
2022
medline:
22
4
2022
entrez:
10
1
2022
Statut:
ppublish
Résumé
MicroRNA-150 (miR-150) plays a protective role in heart failure (HF). Long noncoding RNA, myocardial infarction-associated transcript (MIAT) regulates miR-150 function in vitro by direct interaction. Concurrent with miR-150 downregulation, MIAT is upregulated in failing hearts, and gain-of-function single-nucleotide polymorphisms in MIAT are associated with increased risk of myocardial infarction (MI) in humans. Despite the correlative relationship between MIAT and miR-150 in HF, their in vivo functional relationship has never been established, and molecular mechanisms by which these 2 noncoding RNAs regulate cardiac protection remain elusive. We use MIAT KO (knockout), Using novel mouse models, we demonstrate that genetic overexpression of MIAT worsens cardiac remodeling, while genetic deletion of MIAT protects hearts against MI. Importantly, miR-150 overexpression attenuates the detrimental post-MI effects caused by MIAT. Genome-wide transcriptomic analysis of MIAT null mouse hearts identifies Our findings delineate a pivotal functional interaction among MIAT, miR-150, and
Sections du résumé
BACKGROUND
MicroRNA-150 (miR-150) plays a protective role in heart failure (HF). Long noncoding RNA, myocardial infarction-associated transcript (MIAT) regulates miR-150 function in vitro by direct interaction. Concurrent with miR-150 downregulation, MIAT is upregulated in failing hearts, and gain-of-function single-nucleotide polymorphisms in MIAT are associated with increased risk of myocardial infarction (MI) in humans. Despite the correlative relationship between MIAT and miR-150 in HF, their in vivo functional relationship has never been established, and molecular mechanisms by which these 2 noncoding RNAs regulate cardiac protection remain elusive.
METHODS
We use MIAT KO (knockout),
RESULTS
Using novel mouse models, we demonstrate that genetic overexpression of MIAT worsens cardiac remodeling, while genetic deletion of MIAT protects hearts against MI. Importantly, miR-150 overexpression attenuates the detrimental post-MI effects caused by MIAT. Genome-wide transcriptomic analysis of MIAT null mouse hearts identifies
CONCLUSIONS
Our findings delineate a pivotal functional interaction among MIAT, miR-150, and
Identifiants
pubmed: 35000421
doi: 10.1161/CIRCHEARTFAILURE.121.008686
pmc: PMC9018469
mid: NIHMS1761582
doi:
Substances chimiques
Homeodomain Proteins
0
Hoxa4 protein, mouse
0
MIRN150 microRNA, human
0
Miat long non-coding RNA
0
MicroRNAs
0
Mirn150 microRNA, mouse
0
RNA, Long Noncoding
0
Transcription Factors
0
HOXA4 protein, human
127609-92-1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e008686Subventions
Organisme : American Heart Association-American Stroke Association
ID : 931621
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL146481
Pays : United States
Organisme : American Heart Association-American Stroke Association
ID : 900453
Pays : United States
Organisme : American Heart Association-American Stroke Association
ID : 18TPA34170104
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL124251
Pays : United States
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