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Arch Biochem Biophys ; 705: 108916, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33974917

RESUMO

Noncoding RNAs (ncRNAs) have been shown to play important roles in atherosclerosis-related endothelial cells dysfunction during atherosclerosis processes. In the study, our purpose was to discover new long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) via competitively interacting each other to regulate the pathogenesis process of atherosclerosis. We investigated the roles of lncRNA AK087124 and miR-224-5p in atherosclerotic pathogenesis and found that AK087124 was up-regulated while miR-224-5p was down-regulated in in the plasma and plaque from atherosclerotic mice compared with normal mice. Ox-LDL was used to establish the mouse aorta endothelial cell (MAEC) injury model. The function study indicated that knockdown of AK087124 inhibited ox-LDL induced endothelial apoptosis and inflammatory response. Bioinformatic prediction combining with luciferase assays indicated that AK087124 could sponge miR-224-5p and enhance the PTEN expression which is a target of miR-224-5p. RNA pull down assays also showed that biotin-miR-224-5p probe could interacted directly with AK087124 and PTEN. Pearson correlation analysis further demonstrated that AK087124 and PTEN expression are negatively correlated with miR-224-5p. Rescue study revealed that miR-224-5p silencing and PTEN overexpression both can reverse the effect of AK087124 on the ox-LDL induced endothelial injury. These data indicated that AK087124 and miR-224-5p could be potential biomarkers and target molecules to treatment and diagnosis for atherosclerosis.


Assuntos
Apoptose , Aterosclerose/patologia , Células Endoteliais/patologia , MicroRNAs/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Animais , Aterosclerose/genética , Aterosclerose/metabolismo , Proliferação de Células , Camundongos , Transdução de Sinais
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