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Eur Rev Med Pharmacol Sci ; 24(12): 7024-7032, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32633396

RESUMO

OBJECTIVE: As a result of gene-environment interactions, the incidence of atherosclerosis (AS) is rapidly increasing worldwide. Autophagy in endothelial cells is a key process of AS and is difficult to control when it becomes excessive in the end stage of AS. MATERIALS AND METHODS: In this study, we found increased expression levels of ZNF295-AS1 in the serum of AS patients, as well as in ox-LDL-treated HUVECs. The autophagy level was also upregulated in both samples. We demonstrated that ZNF295-AS1 may interact directly with miR-508-5p to act as a miR-508-5p sponge. The negative relationship between ZNF295-AS1 and miR-508-5p indicated that ZNF295-AS1 may be an upstream suppressor of miR-508-5p. RESULTS: ATG7 plays a critical role in autophagy and was predicted to be a target of miR-508-5p. Therefore, we overexpressed miR-508-5p, which reduced the expression level of ATG7, enhanced cell proliferation and prevented autophagy. These data indicated that the ZNF295-AS1/miR-508-5p/ATG7 axis may participate in autophagy regulation in ox-LDL-treated HUVECs. The subsequent rescue experiments revealed the specificity of the ZNF295-AS1/miR-508-5p/ATG7 axis in the contribution of ZNF295-AS1 to autophagy. CONCLUSIONS: Overall, our findings demonstrate a novel mechanism by which ZNF295-AS1 silencing regulates ATG7 reduction and inhibits autophagy, which may delay the progression of AS. The ZNF295-AS1/miR-508-5p/ATG7 axis may be of therapeutic significance in AS.


Assuntos
Aterosclerose/metabolismo , Proteína 7 Relacionada à Autofagia/metabolismo , Autofagia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Aterosclerose/sangue , Aterosclerose/patologia , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lipoproteínas LDL/farmacologia , RNA Longo não Codificante/sangue
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