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Knockdown of lncRNA HOXA-AS3 Suppresses the Progression of Atherosclerosis via Sponging miR-455-5p
BACKGROUND: Atherosclerosis can lead to multiple cardiovascular diseases, especially myocardial infarction. Long noncoding RNAs (lncRNAs) are involved in multiple diseases, including atherosclerosis. LncRNA HOXA-AS3 was found to be notably upregulated in atherosclerosis. However, the biological func...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490108/ https://www.ncbi.nlm.nih.gov/pubmed/32982172 http://dx.doi.org/10.2147/DDDT.S249830 |
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author | Chi, Kui Zhang, Jinwen Sun, Huanhuan Liu, Yang Li, Ye Yuan, Tao Zhang, Feng |
author_facet | Chi, Kui Zhang, Jinwen Sun, Huanhuan Liu, Yang Li, Ye Yuan, Tao Zhang, Feng |
author_sort | Chi, Kui |
collection | PubMed |
description | BACKGROUND: Atherosclerosis can lead to multiple cardiovascular diseases, especially myocardial infarction. Long noncoding RNAs (lncRNAs) are involved in multiple diseases, including atherosclerosis. LncRNA HOXA-AS3 was found to be notably upregulated in atherosclerosis. However, the biological function of HOXA-AS3 during the occurrence and development of atherosclerosis remains unclear. MATERIALS AND METHODS: Human vascular endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (oxLDL) to mimic atherosclerosis in vitro. Gene and protein expressions in HUVECs were detected by RT-qPCR and Western blot, respectively. Cell proliferation was tested by CCK-8 and Ki67 staining. Cell apoptosis and cycle were measured by flow cytometry. Additionally, the correlation between HOXA-AS3 and miR-455-5p was confirmed by dual luciferase report assay and RNA pull-down. Finally, in vivo model of atherosclerosis was established to confirm the function of HOXA-AS3 during the development of atherosclerosis in vivo. RESULTS: LncRNA HOXA-AS3 was upregulated in oxLDL-treated HUVECs. In addition, oxLDL-induced growth inhibition of HUVECs was significantly reversed by knockdown of HOXA-AS3. Consistently, oxLDL notably induced G1 arrest in HUVECs, while this phenomenon was greatly reversed by HOXA-AS3 siRNA. Furthermore, downregulation of HOXA-AS3 notably inhibited the progression of atherosclerosis through mediation of miR-455-5p/p27 Kip1 axis. Besides, silencing of HOXA-AS3 notably relieved the symptom of atherosclerosis in vivo. CONCLUSION: Downregulation of HOXA-AS3 significantly suppressed the progression of atherosclerosis via regulating miR-455-5p/p27 Kip1 axis. Thus, HOXA-AS3 might serve as a potential target for the treatment of atherosclerosis. |
format | Online Article Text |
id | pubmed-7490108 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-74901082020-09-24 Knockdown of lncRNA HOXA-AS3 Suppresses the Progression of Atherosclerosis via Sponging miR-455-5p Chi, Kui Zhang, Jinwen Sun, Huanhuan Liu, Yang Li, Ye Yuan, Tao Zhang, Feng Drug Des Devel Ther Original Research BACKGROUND: Atherosclerosis can lead to multiple cardiovascular diseases, especially myocardial infarction. Long noncoding RNAs (lncRNAs) are involved in multiple diseases, including atherosclerosis. LncRNA HOXA-AS3 was found to be notably upregulated in atherosclerosis. However, the biological function of HOXA-AS3 during the occurrence and development of atherosclerosis remains unclear. MATERIALS AND METHODS: Human vascular endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (oxLDL) to mimic atherosclerosis in vitro. Gene and protein expressions in HUVECs were detected by RT-qPCR and Western blot, respectively. Cell proliferation was tested by CCK-8 and Ki67 staining. Cell apoptosis and cycle were measured by flow cytometry. Additionally, the correlation between HOXA-AS3 and miR-455-5p was confirmed by dual luciferase report assay and RNA pull-down. Finally, in vivo model of atherosclerosis was established to confirm the function of HOXA-AS3 during the development of atherosclerosis in vivo. RESULTS: LncRNA HOXA-AS3 was upregulated in oxLDL-treated HUVECs. In addition, oxLDL-induced growth inhibition of HUVECs was significantly reversed by knockdown of HOXA-AS3. Consistently, oxLDL notably induced G1 arrest in HUVECs, while this phenomenon was greatly reversed by HOXA-AS3 siRNA. Furthermore, downregulation of HOXA-AS3 notably inhibited the progression of atherosclerosis through mediation of miR-455-5p/p27 Kip1 axis. Besides, silencing of HOXA-AS3 notably relieved the symptom of atherosclerosis in vivo. CONCLUSION: Downregulation of HOXA-AS3 significantly suppressed the progression of atherosclerosis via regulating miR-455-5p/p27 Kip1 axis. Thus, HOXA-AS3 might serve as a potential target for the treatment of atherosclerosis. Dove 2020-09-09 /pmc/articles/PMC7490108/ /pubmed/32982172 http://dx.doi.org/10.2147/DDDT.S249830 Text en © 2020 Chi et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Chi, Kui Zhang, Jinwen Sun, Huanhuan Liu, Yang Li, Ye Yuan, Tao Zhang, Feng Knockdown of lncRNA HOXA-AS3 Suppresses the Progression of Atherosclerosis via Sponging miR-455-5p |
title | Knockdown of lncRNA HOXA-AS3 Suppresses the Progression of Atherosclerosis via Sponging miR-455-5p |
title_full | Knockdown of lncRNA HOXA-AS3 Suppresses the Progression of Atherosclerosis via Sponging miR-455-5p |
title_fullStr | Knockdown of lncRNA HOXA-AS3 Suppresses the Progression of Atherosclerosis via Sponging miR-455-5p |
title_full_unstemmed | Knockdown of lncRNA HOXA-AS3 Suppresses the Progression of Atherosclerosis via Sponging miR-455-5p |
title_short | Knockdown of lncRNA HOXA-AS3 Suppresses the Progression of Atherosclerosis via Sponging miR-455-5p |
title_sort | knockdown of lncrna hoxa-as3 suppresses the progression of atherosclerosis via sponging mir-455-5p |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490108/ https://www.ncbi.nlm.nih.gov/pubmed/32982172 http://dx.doi.org/10.2147/DDDT.S249830 |
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