miR-7a Targets Insulin Receptor Substrate-2 Gene and Suppresses Viability and Invasion of Cells in Diabetic Retinopathy Mice via PI3K-Akt-VEGF Pathway

Zhenyu Ji,1 Jinyuan Luo,1 Ting Su,2 Changzheng Chen,1 Yu Su1 1Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China; 2Eye Institute of Xiamen University, Xiamen University, Xiamen, Fujian, 361102, People’s Republic of C...

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Autores principales:	Ji Z, Luo J, Su T, Chen C, Su Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	mir-7a diabetic retinopathy irs-2 pi3k/akt endothelial cells retinal pericytes. Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/70cb300e066b405495bdcb591956f81c
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spelling	oai:doaj.org-article:70cb300e066b405495bdcb591956f81c2021-12-02T10:52:03ZmiR-7a Targets Insulin Receptor Substrate-2 Gene and Suppresses Viability and Invasion of Cells in Diabetic Retinopathy Mice via PI3K-Akt-VEGF Pathway1178-7007https://doaj.org/article/70cb300e066b405495bdcb591956f81c2021-02-01T00:00:00Zhttps://www.dovepress.com/mir-7a-targets-insulin-receptor-substrate-2-gene-and-suppresses-viabil-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Zhenyu Ji,1 Jinyuan Luo,1 Ting Su,2 Changzheng Chen,1 Yu Su1 1Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China; 2Eye Institute of Xiamen University, Xiamen University, Xiamen, Fujian, 361102, People’s Republic of ChinaCorrespondence: Yu SuDepartment of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of ChinaTel/Fax +86-2788041911Email sy_daisy1206@163.comIntroduction: Diabetic retinopathy (DR) is one of the major leading causes for vision loss globally. Current study illustrates the role of miR-7a in DR.Material and Methods: Retinal pericytes (RPs) and Endothelial cells (ECs) were isolated from mouse model of DR. qRT-PCR was done for expression of miR-7a and target gene mRNA, Western blot for protein expression. Identification of miR-7a target gene was done by TargetScan and Luciferase assay. Cell viability and invasion was done by MTT and Transwell chamber assay.Results: The expression of miR-7a was down-regulated whereas level of IRS-2 was unregulated in isolated RPs and ECs. Luciferase assay suggested correlation between miR-7a and IRS-2, over-expression of miR-7a using a mimic resulted in suppression in viability and invasion capacity of RPs and ECs and inhibited the protein levels of PI3K/Akt cascade and IRS-2, and however the inhibitor reversed them respectively. Transfection of siRNA targeting IRS-2 caused alteration in miR-7a mediated changes in ECs suggesting that miR-7a may decrease angiogenesis in DR by inhibiting the levels of IRS-2.Conclusion: miR-7a suppresses PI3K/Akt cascade via targeting IRS-2, thus decreasing the viability and invasion capacity of RPs and ECs, suggesting an interesting treatment target for DR.Keywords: miR-7a, diabetic retinopathy; DR, IRS-2, PI3K/Akt, endothelial cells; ECs, retinal pericytes; RPsJi ZLuo JSu TChen CSu YDove Medical Pressarticlemir-7adiabetic retinopathyirs-2pi3k/aktendothelial cellsretinal pericytes.Specialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 719-728 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mir-7a diabetic retinopathy irs-2 pi3k/akt endothelial cells retinal pericytes. Specialties of internal medicine RC581-951
spellingShingle	mir-7a diabetic retinopathy irs-2 pi3k/akt endothelial cells retinal pericytes. Specialties of internal medicine RC581-951 Ji Z Luo J Su T Chen C Su Y miR-7a Targets Insulin Receptor Substrate-2 Gene and Suppresses Viability and Invasion of Cells in Diabetic Retinopathy Mice via PI3K-Akt-VEGF Pathway
description	Zhenyu Ji,1 Jinyuan Luo,1 Ting Su,2 Changzheng Chen,1 Yu Su1 1Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China; 2Eye Institute of Xiamen University, Xiamen University, Xiamen, Fujian, 361102, People’s Republic of ChinaCorrespondence: Yu SuDepartment of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of ChinaTel/Fax +86-2788041911Email sy_daisy1206@163.comIntroduction: Diabetic retinopathy (DR) is one of the major leading causes for vision loss globally. Current study illustrates the role of miR-7a in DR.Material and Methods: Retinal pericytes (RPs) and Endothelial cells (ECs) were isolated from mouse model of DR. qRT-PCR was done for expression of miR-7a and target gene mRNA, Western blot for protein expression. Identification of miR-7a target gene was done by TargetScan and Luciferase assay. Cell viability and invasion was done by MTT and Transwell chamber assay.Results: The expression of miR-7a was down-regulated whereas level of IRS-2 was unregulated in isolated RPs and ECs. Luciferase assay suggested correlation between miR-7a and IRS-2, over-expression of miR-7a using a mimic resulted in suppression in viability and invasion capacity of RPs and ECs and inhibited the protein levels of PI3K/Akt cascade and IRS-2, and however the inhibitor reversed them respectively. Transfection of siRNA targeting IRS-2 caused alteration in miR-7a mediated changes in ECs suggesting that miR-7a may decrease angiogenesis in DR by inhibiting the levels of IRS-2.Conclusion: miR-7a suppresses PI3K/Akt cascade via targeting IRS-2, thus decreasing the viability and invasion capacity of RPs and ECs, suggesting an interesting treatment target for DR.Keywords: miR-7a, diabetic retinopathy; DR, IRS-2, PI3K/Akt, endothelial cells; ECs, retinal pericytes; RPs
format	article
author	Ji Z Luo J Su T Chen C Su Y
author_facet	Ji Z Luo J Su T Chen C Su Y
author_sort	Ji Z
title	miR-7a Targets Insulin Receptor Substrate-2 Gene and Suppresses Viability and Invasion of Cells in Diabetic Retinopathy Mice via PI3K-Akt-VEGF Pathway
title_short	miR-7a Targets Insulin Receptor Substrate-2 Gene and Suppresses Viability and Invasion of Cells in Diabetic Retinopathy Mice via PI3K-Akt-VEGF Pathway
title_full	miR-7a Targets Insulin Receptor Substrate-2 Gene and Suppresses Viability and Invasion of Cells in Diabetic Retinopathy Mice via PI3K-Akt-VEGF Pathway
title_fullStr	miR-7a Targets Insulin Receptor Substrate-2 Gene and Suppresses Viability and Invasion of Cells in Diabetic Retinopathy Mice via PI3K-Akt-VEGF Pathway
title_full_unstemmed	miR-7a Targets Insulin Receptor Substrate-2 Gene and Suppresses Viability and Invasion of Cells in Diabetic Retinopathy Mice via PI3K-Akt-VEGF Pathway
title_sort	mir-7a targets insulin receptor substrate-2 gene and suppresses viability and invasion of cells in diabetic retinopathy mice via pi3k-akt-vegf pathway
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/70cb300e066b405495bdcb591956f81c
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miR-7a Targets Insulin Receptor Substrate-2 Gene and Suppresses Viability and Invasion of Cells in Diabetic Retinopathy Mice via PI3K-Akt-VEGF Pathway

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