MicroRNA-30a Regulation of Epithelial-Mesenchymal Transition in Diabetic Cataracts Through Targeting SNAI1

Lu Zhang,Panagiotis A Tsonis,Zhiyuan Li,Lixin Xie,Ye Wang,Wenfeng Li,Yusen Huang

doi:10.1038/s41598-017-01320-3

Abstract

Epithelial-mesenchymal transition (EMT) is a highly conserved and fundamental process in development, fibrosis, and metastasis. During the process, epithelial cells lose their morphology and transcriptional program, and transdifferentiate to mesenchymal cells. It has been reported that lens epithelial cells undergo EMT during cataract formation, and regulation of microRNAs on genes is associated with lens development. However, the molecular mechanisms of this regulation in diabetic cataract still need to be investigated. In the present study, the expression of E-cadherin was downregulated, while the expression of alpha-SMA and vimentin was upregulated in diabetic cataract tissues and the in vitro model, suggesting the involvement of EMT in diabetic cataract formation. Results of miRNA profiling demonstrated that miR-30a was markedly downregulated in diabetic cataract tissues. Overexpression of miR-30a-5p decreased SNAI1, a known modulator of EMT, and the expression of vimentin and alpha-SMA in our diabetic cataract model in vitro. It is concluded that EMT is involved in human diabetic cataract, and upregulation of miR-30a can repress EMT through its targeting of SNAI1 in lens epithelial cells, which make miR-30a a novel target of therapeutic intervention for human diabetic cataract.

Highlights

Lens epithelial cells (LECs) are responsible for differentiation of lens fibers throughout the life of a lens
By immunohistochemistry (Fig. 1B), the protein expression of E-cadherin was found to be higher in normal lens tissues (N) than in diabetic cataract tissues (DCa), while alpha-smooth muscle actin and vimentin showed a higher expression in DCa compared with N
The results revealed a decreased expression of E-cadherin in DCa1 and DCa2 and an increased expression of alpha-SMA and vimentin when compared to N1 and N2

Summary

Introduction

Lens epithelial cells (LECs) are responsible for differentiation of lens fibers throughout the life of a lens. The presence of epithelial-mesenchymal transition (EMT) during epithelial cell differentiation into fiber cells has been reported in the progress of cataract formation[8,9,10,11,12,13]. MicroRNAs (miRNAs) are a group of noncoding small RNAs and have been found to be associated with cell differentiation, proliferation, and apoptosis[14,15,16]. We identified the ectopic expression of miR-30a in diabetic cataract lenses and further investigated the inverted regulation of miR-30a in demotion of EMT by targeting SNAI1 in LECs. we ascertained that miR-30a may play a role in the progress of diabetic cataract formation

Methods

Results

Conclusion