title: Global microRNA expression profiling: curcumin (diferuloylmethane) alters oxidative stress-responsive microRNAs in human ARPE-19 cells.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Howell
authors.forename: Eugene
authors.initials: E
authors.lastname: Chun
authors.forename: Annie N
authors.initials: AN
authors.lastname: Farrell
authors.forename: Elizabeth Y
authors.initials: EY
authors.lastname: Hur
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Caroti
authors.forename: P Michael
authors.initials: PM
authors.lastname: Iuvone
authors.forename: Rashidul
authors.initials: R
authors.lastname: Haque
mesh_terms: D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D016000:Cluster Analysis; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D044139:Receptor, Angiotensin, Type 2; D042461:Vascular Endothelial Growth Factor A; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D003474:Curcumin
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