Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus

Abstract Small non-coding RNAs, in particular microRNAs (miRNAs), regulate fine-tuning of gene expression and can impact a wide range of biological processes. However, their roles in normal and diseased limbal epithelial stem cells (LESC) remain unknown. Using deep sequencing analysis, we investigat...

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Autores principales:	Mangesh Kulkarni, Aleksandra Leszczynska, Gabbie Wei, Michael A. Winkler, Jie Tang, Vincent A. Funari, Nan Deng, Zhenqiu Liu, Vasu Punj, Sophie X. Deng, Alexander V. Ljubimov, Mehrnoosh Saghizadeh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f73e2185d1c44de0b390d473142d5537
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spelling	oai:doaj.org-article:f73e2185d1c44de0b390d473142d55372021-12-02T11:52:25ZGenome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus10.1038/s41598-017-03449-72045-2322https://doaj.org/article/f73e2185d1c44de0b390d473142d55372017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03449-7https://doaj.org/toc/2045-2322Abstract Small non-coding RNAs, in particular microRNAs (miRNAs), regulate fine-tuning of gene expression and can impact a wide range of biological processes. However, their roles in normal and diseased limbal epithelial stem cells (LESC) remain unknown. Using deep sequencing analysis, we investigated miRNA expression profiles in central and limbal regions of normal and diabetic human corneas. We identified differentially expressed miRNAs in limbus vs. central cornea in normal and diabetic (DM) corneas including both type 1 (T1DM/IDDM) and type 2 (T2DM/NIDDM) diabetes. Some miRNAs such as miR-10b that was upregulated in limbus vs. central cornea and in diabetic vs. normal limbus also showed significant increase in T1DM vs. T2DM limbus. Overexpression of miR-10b increased Ki-67 staining in human organ-cultured corneas and proliferation rate in cultured corneal epithelial cells. MiR-10b transfected human organ-cultured corneas showed downregulation of PAX6 and DKK1 and upregulation of keratin 17 protein expression levels. In summary, we report for the first time differential miRNA signatures of T1DM and T2DM corneal limbus harboring LESC and show that miR-10b could be involved in the LESC maintenance and/or their early differentiation. Furthermore, miR-10b upregulation may be an important mechanism of corneal diabetic alterations especially in the T1DM patients.Mangesh KulkarniAleksandra LeszczynskaGabbie WeiMichael A. WinklerJie TangVincent A. FunariNan DengZhenqiu LiuVasu PunjSophie X. DengAlexander V. LjubimovMehrnoosh SaghizadehNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mangesh Kulkarni Aleksandra Leszczynska Gabbie Wei Michael A. Winkler Jie Tang Vincent A. Funari Nan Deng Zhenqiu Liu Vasu Punj Sophie X. Deng Alexander V. Ljubimov Mehrnoosh Saghizadeh Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus
description	Abstract Small non-coding RNAs, in particular microRNAs (miRNAs), regulate fine-tuning of gene expression and can impact a wide range of biological processes. However, their roles in normal and diseased limbal epithelial stem cells (LESC) remain unknown. Using deep sequencing analysis, we investigated miRNA expression profiles in central and limbal regions of normal and diabetic human corneas. We identified differentially expressed miRNAs in limbus vs. central cornea in normal and diabetic (DM) corneas including both type 1 (T1DM/IDDM) and type 2 (T2DM/NIDDM) diabetes. Some miRNAs such as miR-10b that was upregulated in limbus vs. central cornea and in diabetic vs. normal limbus also showed significant increase in T1DM vs. T2DM limbus. Overexpression of miR-10b increased Ki-67 staining in human organ-cultured corneas and proliferation rate in cultured corneal epithelial cells. MiR-10b transfected human organ-cultured corneas showed downregulation of PAX6 and DKK1 and upregulation of keratin 17 protein expression levels. In summary, we report for the first time differential miRNA signatures of T1DM and T2DM corneal limbus harboring LESC and show that miR-10b could be involved in the LESC maintenance and/or their early differentiation. Furthermore, miR-10b upregulation may be an important mechanism of corneal diabetic alterations especially in the T1DM patients.
format	article
author	Mangesh Kulkarni Aleksandra Leszczynska Gabbie Wei Michael A. Winkler Jie Tang Vincent A. Funari Nan Deng Zhenqiu Liu Vasu Punj Sophie X. Deng Alexander V. Ljubimov Mehrnoosh Saghizadeh
author_facet	Mangesh Kulkarni Aleksandra Leszczynska Gabbie Wei Michael A. Winkler Jie Tang Vincent A. Funari Nan Deng Zhenqiu Liu Vasu Punj Sophie X. Deng Alexander V. Ljubimov Mehrnoosh Saghizadeh
author_sort	Mangesh Kulkarni
title	Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus
title_short	Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus
title_full	Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus
title_fullStr	Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus
title_full_unstemmed	Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus
title_sort	genome-wide analysis suggests a differential microrna signature associated with normal and diabetic human corneal limbus
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f73e2185d1c44de0b390d473142d5537
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Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus

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