TGFB3-AS1 promotes Hcy-induced inflammationof macrophages via inhibiting the maturityof miR-144 and upregulating Rap1a

It has been demonstrated that homocysteine (Hcy) can cause inflammatory diseases. Long noncoding RNAs (lncRNA) and microRNAs (miRNAs) are involved in this biological process, but the mechanism underlying Hcy-induced inflammation remains poorly understood. Here, we found that lncRNA TGFB3-AS1 was hig...

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Autores principales:	Hui Zhang, Yinju Hao, Anning Yang, Lin Xie, Ning Ding, Lingbo Xu, Yanhua Wang, Yong Yang, Yongsheng Bai, Huiping Zhang, Yideng Jiang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	homocysteine inflammation lncRNA miRNA Rap1a Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/89ed1b1b7fd7425cb1fe9cc2dfaea80c
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spelling	oai:doaj.org-article:89ed1b1b7fd7425cb1fe9cc2dfaea80c2021-11-22T04:23:53ZTGFB3-AS1 promotes Hcy-induced inflammationof macrophages via inhibiting the maturityof miR-144 and upregulating Rap1a2162-253110.1016/j.omtn.2021.10.031https://doaj.org/article/89ed1b1b7fd7425cb1fe9cc2dfaea80c2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2162253121002742https://doaj.org/toc/2162-2531It has been demonstrated that homocysteine (Hcy) can cause inflammatory diseases. Long noncoding RNAs (lncRNA) and microRNAs (miRNAs) are involved in this biological process, but the mechanism underlying Hcy-induced inflammation remains poorly understood. Here, we found that lncRNA TGFB3-AS1 was highly expressed in macrophages treated with Hcy and the peripheral blood monocytes from cystathionine beta-synthase heterozygous knockout (CBS+/−) mice with a high-methionine diet using lncRNA microarray. In vivo and in vitro experiments further confirmed that TGFB3-AS1 accelerated Hcy-induced inflammation of macrophages through the Rap1a/wnt signaling pathway. Meanwhile, TGFB3-AS1 interacted with Rap1a and reduced degradation of Rap1a through inhibiting its ubiquitination in macrophages treated with Hcy. Rap1a mediated inflammation induced by Hcy and serves as a direct target of miR-144. Moreover, TGFB3-AS1 regulated miR-144 by binding to pri-miR-144 and inhibiting its maturation, which further regulated Rap1a expression. More importantly, we found that high expression of TGFB3-AS1 was positively correlated with the levels of Hcy and proinflammatory cytokines in serum of healthy individuals and patients with HHcy. Our study revealed a novel mechanism by which TGFB3-AS1 promoted inflammation of macrophages through inhibiting miR-144 maturation to stay miR-144 regulated inhibition of functional Rap1a expression.Hui ZhangYinju HaoAnning YangLin XieNing DingLingbo XuYanhua WangYong YangYongsheng BaiHuiping ZhangYideng JiangElsevierarticlehomocysteineinflammationlncRNAmiRNARap1aTherapeutics. PharmacologyRM1-950ENMolecular Therapy: Nucleic Acids, Vol 26, Iss , Pp 1318-1335 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	homocysteine inflammation lncRNA miRNA Rap1a Therapeutics. Pharmacology RM1-950
spellingShingle	homocysteine inflammation lncRNA miRNA Rap1a Therapeutics. Pharmacology RM1-950 Hui Zhang Yinju Hao Anning Yang Lin Xie Ning Ding Lingbo Xu Yanhua Wang Yong Yang Yongsheng Bai Huiping Zhang Yideng Jiang TGFB3-AS1 promotes Hcy-induced inflammationof macrophages via inhibiting the maturityof miR-144 and upregulating Rap1a
description	It has been demonstrated that homocysteine (Hcy) can cause inflammatory diseases. Long noncoding RNAs (lncRNA) and microRNAs (miRNAs) are involved in this biological process, but the mechanism underlying Hcy-induced inflammation remains poorly understood. Here, we found that lncRNA TGFB3-AS1 was highly expressed in macrophages treated with Hcy and the peripheral blood monocytes from cystathionine beta-synthase heterozygous knockout (CBS+/−) mice with a high-methionine diet using lncRNA microarray. In vivo and in vitro experiments further confirmed that TGFB3-AS1 accelerated Hcy-induced inflammation of macrophages through the Rap1a/wnt signaling pathway. Meanwhile, TGFB3-AS1 interacted with Rap1a and reduced degradation of Rap1a through inhibiting its ubiquitination in macrophages treated with Hcy. Rap1a mediated inflammation induced by Hcy and serves as a direct target of miR-144. Moreover, TGFB3-AS1 regulated miR-144 by binding to pri-miR-144 and inhibiting its maturation, which further regulated Rap1a expression. More importantly, we found that high expression of TGFB3-AS1 was positively correlated with the levels of Hcy and proinflammatory cytokines in serum of healthy individuals and patients with HHcy. Our study revealed a novel mechanism by which TGFB3-AS1 promoted inflammation of macrophages through inhibiting miR-144 maturation to stay miR-144 regulated inhibition of functional Rap1a expression.
format	article
author	Hui Zhang Yinju Hao Anning Yang Lin Xie Ning Ding Lingbo Xu Yanhua Wang Yong Yang Yongsheng Bai Huiping Zhang Yideng Jiang
author_facet	Hui Zhang Yinju Hao Anning Yang Lin Xie Ning Ding Lingbo Xu Yanhua Wang Yong Yang Yongsheng Bai Huiping Zhang Yideng Jiang
author_sort	Hui Zhang
title	TGFB3-AS1 promotes Hcy-induced inflammationof macrophages via inhibiting the maturityof miR-144 and upregulating Rap1a
title_short	TGFB3-AS1 promotes Hcy-induced inflammationof macrophages via inhibiting the maturityof miR-144 and upregulating Rap1a
title_full	TGFB3-AS1 promotes Hcy-induced inflammationof macrophages via inhibiting the maturityof miR-144 and upregulating Rap1a
title_fullStr	TGFB3-AS1 promotes Hcy-induced inflammationof macrophages via inhibiting the maturityof miR-144 and upregulating Rap1a
title_full_unstemmed	TGFB3-AS1 promotes Hcy-induced inflammationof macrophages via inhibiting the maturityof miR-144 and upregulating Rap1a
title_sort	tgfb3-as1 promotes hcy-induced inflammationof macrophages via inhibiting the maturityof mir-144 and upregulating rap1a
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/89ed1b1b7fd7425cb1fe9cc2dfaea80c
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TGFB3-AS1 promotes Hcy-induced inflammationof macrophages via inhibiting the maturityof miR-144 and upregulating Rap1a

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