title: Polycomb repressive complex 2 regulates MiR-200b in retinal endothelial cells: potential relevance in diabetic retinopathy.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.
authors.forename: Michael Anthony
authors.initials: MA
authors.lastname: Ruiz
authors.affiliation: Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.
authors.forename: Biao
authors.initials: B
authors.lastname: Feng
authors.affiliation: Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.
authors.forename: Subrata
authors.initials: S
authors.lastname: Chakrabarti
mesh_terms: D000818:Animals; D002460:Cell Line; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A; D063151:Polycomb Repressive Complex 2; D005947:Glucose