title: Effect of nitric oxide on microRNA-155 expression in human hepatic epithelial cells.
abstract: OBJECTIVE
  Nitric oxide (NO) is a signaling molecule and regulator of immunity and inflammation. MicroRNAs (miRNAs) regulate gene transcription and are involved in inflammatory processes and cancer. This study sought to determine if NO activity affects miRNA expression.
  
  
  METHODS
  Human liver epithelial (HepG2) cells were treated with the NO-releasing S-nitroso-N-acetylpenicillamine (SNAP) 100 μM for 4 h and subjected to microarray analysis. To examine the underlying mechanisms, cells were exposed to cGMP analog 8-bromo-cGMP, protein kinase inhibitor Rp-*-Br-PET-cGMPS (Rp-PET), or nitric synthase inhibitor L-NAME and evaluated with RT-PCR.
  
  
  RESULTS
  MiR-155 was the only miRNA of the 887 arrayed that showed a change in expression after SNAP treatment. Incubation of the cells with 8-bromo-cGMP increased miR-155 expression 4.0 ± 0.7-fold (p < 0.05); Rp-PET before SNAP had a dual, concentration-dependent effect. SNAP treatment induced a 3.1 ± 0.7-fold change in miRNA-155 expression, Rp-PET 25 μM, a 7.3 ± 2.2-fold change, and Rp-PET 100 μM, a 0.79 ± 0.09-fold change (SNAP vs SNAP + Rp-PET, p < 0.05). In unstimulated cells, Rp-PET or L-NAME treatment increased miR-155 expression by 3.5 ± 0.7-fold and 5.6 ± 2.2-fold, respectively (p < 0.05).
  
  
  CONCLUSIONS
  In HepG2 cells, exogenous NO increases miR-155 expression, but endogenous basal NO inhibits it. Both effects are mediated via cGMP/PKG signaling. The upregulation of miR-155 by NO provides a new link between NO, inflammation, and cancer.
authors.affiliation: Infectious Diseases Research Laboratory, Felsenstein Medical Research Center, Beilinson Campus, 49100, Petach Tikva, Israel, yuhas@post.tau.ac.il.
authors.forename: Yael
authors.initials: Y
authors.lastname: Yuhas
authors.forename: Eva
authors.initials: E
authors.lastname: Berent
authors.forename: Shai
authors.initials: S
authors.lastname: Ashkenazi
mesh_terms: D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000166:cytology; D035683:MicroRNAs / Q000235:genetics*; D009569:Nitric Oxide / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D009569:Nitric Oxide