Global microRNA expression profiling: Curcumin (diferuloylmethane) alters oxidative stress-responsive microRNAs in human ARPE-19 cells

• Type of Material: Article
• Authors: Jennifer Christina Howell, Emory University; Eugene Chun, Emory University; Annie N. Farrell, Emory University; Elizabeth Y. Hur, Emory University; Courtney M. Caroti, Emory University; P Michael Iuvone, Emory University; Rashidul Haque, Emory University
• Language: English
• Date: 2013-03-15
• Publisher: Emory University
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Molecular Vision
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://www.molvis.org/molvis/v19/544/
• Title of Journal or Parent Work: Molecular Vision
• Volume: 19
• Start Page: 544
• End Page: 560
• Research Categories: Health Sciences, Opthamology

Abstract

Purpose: In recent years, microRNAs (miRNAs) have been reported to play important roles in a broad range of biologic processes, including oxidative stress-mediated ocular diseases. In addition, the polyphenolic compound curcumin has been shown to possess anti-inflammatory, antioxidant, anticancer, antiproliferative, and proapoptotic activities. The aim of this study was to investigate the impact of curcumin on the expression profiles of miRNAs in ARPE-19 cells exposed to oxidative stress. Methods: MiRNA expression profiles were measured in ARPE-19 cells treated with 20 μΜ curcumin and 200 μΜ H2O2. PCR array analysis was performed using web-based software from SABiosciences. The cytotoxicity of ARPE-19 cells was determined with the CellTiter-Blue cell viability assay. The effects of curcumin on potential miRNA targets were analyzed with quantitative real-time PCR and western blotting. Results: Curcumin treatment alone for 6 h had no effect on ARPE-19 cell viability. Incubation with H2O2 (200 µM) alone for 18 h decreased cell viability by 12.5%. Curcumin alone downregulated 20 miRNAs and upregulated nine miRNAs compared with controls. H2O2 downregulated 18 miRNAs and upregulated 29 miRNAs. Furthermore, curcumin pretreatment in cells exposed to H2O2 significantly reduced the H2O2-induced expression of 17 miRNAs. As determined with quantitative real-time PCR and western blotting, curcumin increased the expression of antioxidant genes and reduced angiotensin II type 1 receptor, nuclear factor-kappa B, and vascular endothelial growth factor expression at the messenger RNA and protein levels. Conclusions: The results demonstrated that curcumin alters the expression of H2O2-modulated miRNAs that are putative regulators of antioxidant defense and renin-angiotensin systems, which have been reported to be linked to ocular diseases.