Polycomb repressive complex 2 regulates MiR-200b in retinal endothelial cells: potential relevance in diabetic retinopathy.

Ruiz MA, Feng B, Chakrabarti S
Source: PLoS ONE
Publication Date: (2015)
Issue: 10(4): e0123987
Cells used in publication:
Endothelial, MV dermal (HMVEC-d), human
Species: human
Tissue Origin: dermal
Researchers investigated Polycomb Repressive Complex 2 (PRC2) in regards to its potential role in diabetic retinopathy. Cells were exposed to high levels of glucose. Then the cells were analyzed for MiR-200b and VEGF as well as PRC2. Lonza\\\'s normal dermal HMVECs and diabietic dermal HMVECs were used in this study.
Glucose-induced augmented vascular endothelial growth factor (VEGF) production is a key event in diabetic retinopathy. We have previously demonstrated that downregulation of miR-200b increases VEGF, mediating structural and functional changes in the retina in diabetes. However, mechanisms regulating miR-200b in diabetes are not known. Histone methyltransferase complex, Polycomb Repressive Complex 2 (PRC2), has been shown to repress miRNAs in neoplastic process. We hypothesized that, in diabetes, PRC2 represses miR-200b through its histone H3 lysine-27 trimethylation mark. We show that human retinal microvascular endothelial cells exposed to high levels of glucose regulate miR-200b repression through histone methylation and that inhibition of PRC2 increases miR-200b while reducing VEGF. Furthermore, retinal tissue from animal models of diabetes showed increased expression of major PRC2 components, demonstrating in vivo relevance. This research established a repressive relationship between PRC2 and miR-200b, providing evidence of a novel mechanism of miRNA regulation through histone methylation.