MicroRNA-27a Promotes Oxidative-Induced RPE Cell Death through Targeting FOXO1

Age-related macular degeneration (AMD) is a multifactor disease, which is primarily characterized by retinal pigment epithelium (RPE) cell loss. Since the retina is the most metabolically active tissue, RPE cells are exposed to consistent oxidative environment. So, oxidation-induced RPE cell death h...

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Autores principales:	Chengda Ren, Weinan Hu, Qingquan Wei, Wenting Cai, Huizi Jin, Donghui Yu, Chang Liu, Tianyi Shen, Meijiang Zhu, Xiuwei Liang, Jing Yu
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/ef353419ef40401db11851df3a90233a
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spelling	oai:doaj.org-article:ef353419ef40401db11851df3a90233a2021-11-15T01:19:51ZMicroRNA-27a Promotes Oxidative-Induced RPE Cell Death through Targeting FOXO12314-614110.1155/2021/6666506https://doaj.org/article/ef353419ef40401db11851df3a90233a2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/6666506https://doaj.org/toc/2314-6141Age-related macular degeneration (AMD) is a multifactor disease, which is primarily characterized by retinal pigment epithelium (RPE) cell loss. Since the retina is the most metabolically active tissue, RPE cells are exposed to consistent oxidative environment. So, oxidation-induced RPE cell death has long been considered a contributor to the onset of AMD. Here, we applied a retinal degeneration (RD) rat model induced by blue light-emitting diode (LED) and a cell model constructed by H2O2 stimulus to mimic the prooxidant environment of the retina. We detected that the expression of miR-27a was upregulated and the expression of FOXO1 was downregulated in both models. So, we furtherly investigated the role of miR-27a-FOXO1 axis in RPE in protesting against oxidants. Lentivirus-mediated RNA was injected intravitreally into rats to modulate the miR-27a-FOXO1 axis. Retinal function and histopathological changes were evaluated by electroretinography (ERG) analysis and hematoxylin and eosin (H&E) staining, respectively. Massive photoreceptor and RPE cell death were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The damage to the retina was aggravated in the FOXO1 gene-knockdown and miR-27a-overexpression groups after exposure to LED but was alleviated in the FOXO1 gene-overexpression or miR-27a-knockdown groups. Dual luciferase assay was used to detect the binding site of miR-27a and FOXO1. Upregulated miR-27a inhibited the expression of FOXO1 by directly binding to the FOXO1 mRNA 3′UTR and decreased the autophagy activity of ARPE-19 cells, resulting in the accumulation of reactive oxygen species (ROS) and decrease of cell viability. The results suggest that miR-27a is a negative regulator of FOXO1. Also, our data emphasize the prominent role of miR-27a/FOXO1 axis in modulating ROS accumulation and cell death in RPE cell model under oxidative stress and influencing the retinal function in the LED-induced RD rat model.Chengda RenWeinan HuQingquan WeiWenting CaiHuizi JinDonghui YuChang LiuTianyi ShenMeijiang ZhuXiuwei LiangJing YuHindawi LimitedarticleMedicineRENBioMed Research International, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Chengda Ren Weinan Hu Qingquan Wei Wenting Cai Huizi Jin Donghui Yu Chang Liu Tianyi Shen Meijiang Zhu Xiuwei Liang Jing Yu MicroRNA-27a Promotes Oxidative-Induced RPE Cell Death through Targeting FOXO1
description	Age-related macular degeneration (AMD) is a multifactor disease, which is primarily characterized by retinal pigment epithelium (RPE) cell loss. Since the retina is the most metabolically active tissue, RPE cells are exposed to consistent oxidative environment. So, oxidation-induced RPE cell death has long been considered a contributor to the onset of AMD. Here, we applied a retinal degeneration (RD) rat model induced by blue light-emitting diode (LED) and a cell model constructed by H2O2 stimulus to mimic the prooxidant environment of the retina. We detected that the expression of miR-27a was upregulated and the expression of FOXO1 was downregulated in both models. So, we furtherly investigated the role of miR-27a-FOXO1 axis in RPE in protesting against oxidants. Lentivirus-mediated RNA was injected intravitreally into rats to modulate the miR-27a-FOXO1 axis. Retinal function and histopathological changes were evaluated by electroretinography (ERG) analysis and hematoxylin and eosin (H&E) staining, respectively. Massive photoreceptor and RPE cell death were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The damage to the retina was aggravated in the FOXO1 gene-knockdown and miR-27a-overexpression groups after exposure to LED but was alleviated in the FOXO1 gene-overexpression or miR-27a-knockdown groups. Dual luciferase assay was used to detect the binding site of miR-27a and FOXO1. Upregulated miR-27a inhibited the expression of FOXO1 by directly binding to the FOXO1 mRNA 3′UTR and decreased the autophagy activity of ARPE-19 cells, resulting in the accumulation of reactive oxygen species (ROS) and decrease of cell viability. The results suggest that miR-27a is a negative regulator of FOXO1. Also, our data emphasize the prominent role of miR-27a/FOXO1 axis in modulating ROS accumulation and cell death in RPE cell model under oxidative stress and influencing the retinal function in the LED-induced RD rat model.
format	article
author	Chengda Ren Weinan Hu Qingquan Wei Wenting Cai Huizi Jin Donghui Yu Chang Liu Tianyi Shen Meijiang Zhu Xiuwei Liang Jing Yu
author_facet	Chengda Ren Weinan Hu Qingquan Wei Wenting Cai Huizi Jin Donghui Yu Chang Liu Tianyi Shen Meijiang Zhu Xiuwei Liang Jing Yu
author_sort	Chengda Ren
title	MicroRNA-27a Promotes Oxidative-Induced RPE Cell Death through Targeting FOXO1
title_short	MicroRNA-27a Promotes Oxidative-Induced RPE Cell Death through Targeting FOXO1
title_full	MicroRNA-27a Promotes Oxidative-Induced RPE Cell Death through Targeting FOXO1
title_fullStr	MicroRNA-27a Promotes Oxidative-Induced RPE Cell Death through Targeting FOXO1
title_full_unstemmed	MicroRNA-27a Promotes Oxidative-Induced RPE Cell Death through Targeting FOXO1
title_sort	microrna-27a promotes oxidative-induced rpe cell death through targeting foxo1
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/ef353419ef40401db11851df3a90233a
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MicroRNA-27a Promotes Oxidative-Induced RPE Cell Death through Targeting FOXO1

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