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 language | English (US) |
|---|---|
| Article number | 3448 |
| Journal | Scientific reports |
| Volume | 7 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2017 |
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All Science Journal Classification (ASJC) codes
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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 journal › Article
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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U2 - 10.1038/s41598-017-03449-7
DO - 10.1038/s41598-017-03449-7
M3 - Article
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 3448
ER -