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lncRNA CASC7 regulates pathological progression of ox-LDL-stimulated atherosclerotic cell models via sponging miR-21 and regulating PI3K/Akt and TLR4/NF-κB signaling pathways

Atherosclerosis (AS) is a frequently occurring cause of cardiovascular disease and involves a complicated pathophysiological process. Studies suggest that long non-coding RNAs (lncRNAs) are involved in AS genesis and progression, but mechanisms underlying these connections are unclear. Therefore, th...

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Autores principales: Pei, Xueliang, Wen, Yongjin, Cui, Facai, Yang, Zhiyuan, Xie, Zhouliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714147/
https://www.ncbi.nlm.nih.gov/pubmed/34887360
http://dx.doi.org/10.18632/aging.203757
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author Pei, Xueliang
Wen, Yongjin
Cui, Facai
Yang, Zhiyuan
Xie, Zhouliang
author_facet Pei, Xueliang
Wen, Yongjin
Cui, Facai
Yang, Zhiyuan
Xie, Zhouliang
author_sort Pei, Xueliang
collection PubMed
description Atherosclerosis (AS) is a frequently occurring cause of cardiovascular disease and involves a complicated pathophysiological process. Studies suggest that long non-coding RNAs (lncRNAs) are involved in AS genesis and progression, but mechanisms underlying these connections are unclear. Therefore, this work focused on exploring the role of lncRNA CASC7 in AS. In this study, RNA-seq sequencing results identified 1040 lncRNAs differentially expressed between AS patients and healthy controls. Of these lncRNAs, 458 were up-regulated and 582 were downregulated. CASC7 was found to be down-regulated in serum samples from AS patients and in HUVEC and VSMC exposed to ox-LDL. Overexpression of CASC7 inhibited proliferation and enhanced apoptosis of VSMC, and it markedly reduced IL-1β, IL-6 and TNF-α levels in HUVEC. Increased expression of a CASC7 target, miR-21, abolished the effects of CASC7 on HUVEC and VSMC. Notably, miR-21 targets PI3K in VSMC and TLR4 in HUVEC. The inhibitory effect of CASC7 was decreased by stimulation of PI3K, suggesting that the CASC7/miR-21 axis functions through PI3K/Akt signaling in VSMC. Similarly, the inhibitory effect of CASC7 on the inflammatory response in HUVEC was abolished through activating the TLR4/NF-κB signaling pathway. CASC7 inhibited proliferation and enhanced the apoptosis of VSMC through modulating the miR-21/PI3K-AKT axis, and upregulating CASC7 suppressed the inflammatory response of HUVEC by sponging miR-21 to inhibit the TLR4/NF-κB signal pathway.
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spelling pubmed-87141472021-12-29 lncRNA CASC7 regulates pathological progression of ox-LDL-stimulated atherosclerotic cell models via sponging miR-21 and regulating PI3K/Akt and TLR4/NF-κB signaling pathways Pei, Xueliang Wen, Yongjin Cui, Facai Yang, Zhiyuan Xie, Zhouliang Aging (Albany NY) Research Paper Atherosclerosis (AS) is a frequently occurring cause of cardiovascular disease and involves a complicated pathophysiological process. Studies suggest that long non-coding RNAs (lncRNAs) are involved in AS genesis and progression, but mechanisms underlying these connections are unclear. Therefore, this work focused on exploring the role of lncRNA CASC7 in AS. In this study, RNA-seq sequencing results identified 1040 lncRNAs differentially expressed between AS patients and healthy controls. Of these lncRNAs, 458 were up-regulated and 582 were downregulated. CASC7 was found to be down-regulated in serum samples from AS patients and in HUVEC and VSMC exposed to ox-LDL. Overexpression of CASC7 inhibited proliferation and enhanced apoptosis of VSMC, and it markedly reduced IL-1β, IL-6 and TNF-α levels in HUVEC. Increased expression of a CASC7 target, miR-21, abolished the effects of CASC7 on HUVEC and VSMC. Notably, miR-21 targets PI3K in VSMC and TLR4 in HUVEC. The inhibitory effect of CASC7 was decreased by stimulation of PI3K, suggesting that the CASC7/miR-21 axis functions through PI3K/Akt signaling in VSMC. Similarly, the inhibitory effect of CASC7 on the inflammatory response in HUVEC was abolished through activating the TLR4/NF-κB signaling pathway. CASC7 inhibited proliferation and enhanced the apoptosis of VSMC through modulating the miR-21/PI3K-AKT axis, and upregulating CASC7 suppressed the inflammatory response of HUVEC by sponging miR-21 to inhibit the TLR4/NF-κB signal pathway. Impact Journals 2021-12-09 /pmc/articles/PMC8714147/ /pubmed/34887360 http://dx.doi.org/10.18632/aging.203757 Text en Copyright: © 2021 Pei et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Pei, Xueliang
Wen, Yongjin
Cui, Facai
Yang, Zhiyuan
Xie, Zhouliang
lncRNA CASC7 regulates pathological progression of ox-LDL-stimulated atherosclerotic cell models via sponging miR-21 and regulating PI3K/Akt and TLR4/NF-κB signaling pathways
title lncRNA CASC7 regulates pathological progression of ox-LDL-stimulated atherosclerotic cell models via sponging miR-21 and regulating PI3K/Akt and TLR4/NF-κB signaling pathways
title_full lncRNA CASC7 regulates pathological progression of ox-LDL-stimulated atherosclerotic cell models via sponging miR-21 and regulating PI3K/Akt and TLR4/NF-κB signaling pathways
title_fullStr lncRNA CASC7 regulates pathological progression of ox-LDL-stimulated atherosclerotic cell models via sponging miR-21 and regulating PI3K/Akt and TLR4/NF-κB signaling pathways
title_full_unstemmed lncRNA CASC7 regulates pathological progression of ox-LDL-stimulated atherosclerotic cell models via sponging miR-21 and regulating PI3K/Akt and TLR4/NF-κB signaling pathways
title_short lncRNA CASC7 regulates pathological progression of ox-LDL-stimulated atherosclerotic cell models via sponging miR-21 and regulating PI3K/Akt and TLR4/NF-κB signaling pathways
title_sort lncrna casc7 regulates pathological progression of ox-ldl-stimulated atherosclerotic cell models via sponging mir-21 and regulating pi3k/akt and tlr4/nf-κb signaling pathways
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714147/
https://www.ncbi.nlm.nih.gov/pubmed/34887360
http://dx.doi.org/10.18632/aging.203757
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