The long noncoding RNA NR_045363 involves cardiomyocyte apoptosis and cardiac repair via p53 signal pathway.
apoptosis
heart function
ingenuity pathway analysis
long noncoding RNA
myocardial infarction
p53 signaling pathway
Journal
Cell biology international
ISSN: 1095-8355
Titre abrégé: Cell Biol Int
Pays: England
ID NLM: 9307129
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
16
09
2019
revised:
30
04
2020
accepted:
05
05
2020
pubmed:
7
5
2020
medline:
23
6
2021
entrez:
7
5
2020
Statut:
ppublish
Résumé
Long noncoding RNAs (lncRNAs) can participate in various biological behaviors, including regulating cell differentiation, proliferation, and apoptosis. The investigators have previously confirmed that highly conserved lncRNA NR_045363 controls cardiomyocyte (CM) proliferation and cardiac repair. The present study investigates the effects of NR_045363 on CM apoptosis. Seven-day-old mice were subjected to permanent left anterior descending coronary artery ligation (LAD), and the NR_045363 expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of NR_045363 in the MI group significantly exceeded the Sham group during the first week after the operation. The NR_045363 expression was knocked down in primary cultured CMs using an NR_045363-targeting lncRNA Smart silencer, and the apoptosis of CMs was analyzed by terminal-deoxynucleoitidyl transferase mediated nick end labeling and Annexin-V/PI double staining. These present results indicate that the NR_045363 knockdown significantly promoted the apoptosis of CMs. In order to investigate the underlying mechanism, RNA-sequencing (RNA-seq) was performed, and ingenuity pathway analysis (IPA) was used to analyze the RNA-seq results. The RNA-seq data revealed that a total of 2,291 genes were upregulated or downregulated in NR_045363 knockdown CMs, and the IPA analysis indicated that tumor protein 53 (p53) was the upstream regulator. In vivo, the NR_045363 overexpression through the AAV9 system improved the heart function after MI in 7-day-old mice and inhibited the CM apoptosis. These data suggest that NR_045363 is involved in CM apoptosis and that NR_045363 overexpression exerts positive effects on cardiac repair by alleviating CM apoptosis through the inhibition of the p53 pathway.
Substances chimiques
RNA, Long Noncoding
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1957-1965Subventions
Organisme : Natural Science Foundation of Beijing Municipality
ID : 7172183
Organisme : National Natural Science Foundation of China
ID : 81670255
Organisme : National Natural Science Foundation of China
ID : 81770308
Organisme : Natural Science Foundation of Zhejiang Province
ID : LY14H020008
Organisme : CAMS Innovation Fund for Medical Sciences
ID : 2016-I2M-1-015
Informations de copyright
© 2020 International Federation for Cell Biology.
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