Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus.
Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus.
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DOI：
10.1038/s41598-017-03449-7
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发表时间：
2017-06-14
影响因子：
4.6
通讯作者：
Saghizadeh M
中科院分区：
文献类型：
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作者：
Kulkarni M;Leszczynska A;Wei G;Winkler MA;Tang J;Funari VA;Deng N;Liu Z;Punj V;Deng SX;Ljubimov AV;Saghizadeh M
小的非编码RNAs，特别是microRNAs(MiRNAs)，调节基因表达的微调，可以影响广泛的生物过程。然而，它们在正常和病变的角膜缘上皮干细胞(LESC)中的作用仍不清楚。使用深度测序分析，我们研究了正常和糖尿病人角膜中央和边缘区域的miRNA表达谱。我们鉴定了在正常和糖尿病(DM)角膜，包括1型(T1 DM/IDDM)和2型(T2 DM/NIDDM)的角膜边缘和中央角膜中差异表达的miRNAs。一些miRNAs，如miR-10b，在角膜缘相对于中央角膜，在糖尿病角膜缘与正常角膜缘中表达上调，在T1 DM与T2 DM的角膜缘中也有显著增加。MiR-10b的过表达增加了人器官培养的角膜Ki-67染色和培养的角膜上皮细胞的增殖率。MIR-10b转染人器官培养角膜后，PAX6和Dkk1表达下调，角蛋白17蛋白表达上调。综上所述，我们首次报道了携带LESC的T1 DM和T2 DM角膜缘的差异miRNA信号，并表明miR-10b可能参与了LESC的维持和/或其早期分化。此外，miR-10b上调可能是糖尿病角膜病变的一个重要机制，尤其是在T1 DM患者中。
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.