MicroRNA-26a and -26b inhibit lens fibrosis and cataract by negatively regulating Jagged-1/Notch signaling pathway This article has been corrected since Online Publication and an erratum has also been Published

• Published in: Cell death and differentiation Vol. 24; no. 8; pp. 1431 - 1442
• Main Authors: Chen, Xiaoyun, Xiao, Wei, Chen, Weirong, Liu, Xialin, Wu, Mingxing, Bo, Qu, Luo, Yan, Ye, Shaobi, Cao, Yihai, Liu, Yizhi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.06.2017
• Subjects: 631/80; 692/308/1426; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Cycle Analysis; Life Sciences; original-paper; Stem Cells
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/cdd.2016.152

Fibrosis is a chronic process involving development and progression of multiple diseases in various organs and is responsible for almost half of all known deaths. Epithelial–mesenchymal transition (EMT) is the vital process in organ fibrosis. Lens is an elegant biological tool to investigate the fibrosis process because of its unique biological properties. Using gain- and loss-of-function assays, and different lens fibrosis models, here we demonstrated that microRNA (miR)-26a and miR-26b, members of the miR-26 family have key roles in EMT and fibrosis. They can significantly inhibit proliferation, migration, EMT of lens epithelial cells and lens fibrosis in vitro and in vivo . Interestingly, we revealed that the mechanisms of anti-EMT effects of miR-26a and -26b are via directly targeting Jagged-1 and suppressing Jagged-1/Notch signaling. Furthermore, we provided in vitro and in vivo evidence that Jagged-1/Notch signaling is activated in TGF β 2-stimulated EMT, and blockade of Notch signaling can reverse lens epithelial cells (LECs) EMT and lens fibrosis. Given the general involvement of EMT in most fibrotic diseases, cancer metastasis and recurrence, miR-26 family and Notch pathway may have therapeutic uses in treating fibrotic diseases and cancers.