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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article number3448
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Limbus Corneae
MicroRNAs
Cornea
Genome
Epithelial Cells
Stem Cells
Keratin-17
Up-Regulation
Biological Phenomena
High-Throughput Nucleotide Sequencing
Small Untranslated RNA
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Down-Regulation
Maintenance
Staining and Labeling
Gene Expression

All Science Journal Classification (ASJC) codes

  • General

Cite this

Kulkarni, M., Leszczynska, A., Wei, G., Winkler, M. A., Tang, J., Funari, V. A., ... Saghizadeh, M. (2017). Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus. Scientific reports, 7(1), [3448]. https://doi.org/10.1038/s41598-017-03449-7
Kulkarni, Mangesh ; Leszczynska, Aleksandra ; Wei, Gabbie ; Winkler, Michael A. ; Tang, Jie ; Funari, Vincent A. ; Deng, Nan ; Liu, Zhenqiu ; Punj, Vasu ; Deng, Sophie X. ; Ljubimov, Alexander V. ; Saghizadeh, Mehrnoosh. / Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus. In: Scientific reports. 2017 ; Vol. 7, No. 1.
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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.",
author = "Mangesh Kulkarni and Aleksandra Leszczynska and Gabbie Wei and Winkler, {Michael A.} and Jie Tang and Funari, {Vincent A.} and Nan Deng and Zhenqiu Liu and Vasu Punj and Deng, {Sophie X.} and Ljubimov, {Alexander V.} and Mehrnoosh Saghizadeh",
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Kulkarni, M, Leszczynska, A, Wei, G, Winkler, MA, Tang, J, Funari, VA, Deng, N, Liu, Z, Punj, V, Deng, SX, Ljubimov, AV & Saghizadeh, M 2017, 'Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus', Scientific reports, vol. 7, no. 1, 3448. https://doi.org/10.1038/s41598-017-03449-7

Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus. / Kulkarni, Mangesh; Leszczynska, Aleksandra; Wei, Gabbie; Winkler, Michael A.; Tang, Jie; Funari, Vincent A.; Deng, Nan; Liu, Zhenqiu; Punj, Vasu; Deng, Sophie X.; Ljubimov, Alexander V.; Saghizadeh, Mehrnoosh.

In: Scientific reports, Vol. 7, No. 1, 3448, 01.12.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus

AU - Kulkarni, Mangesh

AU - Leszczynska, Aleksandra

AU - Wei, Gabbie

AU - Winkler, Michael A.

AU - Tang, Jie

AU - Funari, Vincent A.

AU - Deng, Nan

AU - Liu, Zhenqiu

AU - Punj, Vasu

AU - Deng, Sophie X.

AU - Ljubimov, Alexander V.

AU - Saghizadeh, Mehrnoosh

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

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