title: Intracellular and extracellular miRNome deregulation in cellular models of NAFLD or NASH: Clinical implications.
abstract: Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD has the potential to progress through the inflammatory phase of nonalcoholic steatohepatitis (NASH) to fibrosis, cirrhosis, and hepatocellular carcinoma. Identifying patients at risk for this transition is a relevant clinical challenge. The complexity of these phenotypes in vivo made necessary the development of in vitro models in order to dissect the molecular signalling affected in NAFLD and NASH, but also to identify potential circulating biomarkers.
  
  
  
  We profiled the expression of 754 cellular and medium-secreted human miRNAs in HepG2 cells after lipotoxic (Palmitate, model of NASH) or not-lipotoxic stimuli (Oleate-Palmitate, model of NAFLD). Results were validated through Single TaqMan assays. We performed computational analysis of miRNA targets and pathways. Oleate-palmitate treatment induced a variation of 2.8% and 10% of total miRNAs in cells and medium, respectively; palmitate treatment caused 10% and 19% intracellular and extracellular miRNA deregulation, respectively. We validated miR-126, miR-150, miR-223, miR-483-3p, miR-1226*, and miR-1290 deregulation. Through computational analysis, we observed that targets of both intracellular and extracellular DE miRNAs were involved in processes associated with the onset and progression of NAFLD and NASH, such as fatty acid metabolism, apoptosis and inflammation.
  
  
  
  These data would be useful to elucidate the role of miRNAs in the pathogenesis and progression of the NAFLD spectrum, but they also allow the identification of novel potential biomarkers for differential diagnosis to be tested in vivo.
authors.affiliation: Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Di Mauro
authors.affiliation: Department of BioMedical Sciences and BioTechnology, Section of Biology and Genetics Giovanni Sichel, Unit of BioMolecular, Genome and Complex Systems BioMedicine, Catania, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ragusa
authors.affiliation: Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Urbano
authors.affiliation: Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Filippello
authors.affiliation: Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Di Pino
authors.affiliation: Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Scamporrino
authors.affiliation: Department of Clinical and Experimental Medicine, Bioinformatics, University of Catania, Catania, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pulvirenti
authors.affiliation: Department of Clinical and Experimental Medicine, Bioinformatics, University of Catania, Catania, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ferro
authors.affiliation: Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Rabuazzo
authors.affiliation: Department of BioMedical Sciences and BioTechnology, Section of Biology and Genetics Giovanni Sichel, Unit of BioMolecular, Genome and Complex Systems BioMedicine, Catania, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Purrello
authors.affiliation: Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania, Italy. Electronic address: fpurrell@unict.it.
authors.forename: F
authors.initials: F
authors.lastname: Purrello
authors.affiliation: Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Piro
mesh_terms: D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; D002518:Ceramides / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology; D004075:Diglycerides / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019301:Oleic Acid / Q000633:toxicity; D020411:Oligonucleotide Array Sequence Analysis; D019308:Palmitic Acid / Q000633:toxicity; D010766:Phosphorylation; D060066:Protein Interaction Maps; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D018955:CD36 Antigens; D002518:Ceramides; D004075:Diglycerides; D005819:Genetic Markers; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D035683:MicroRNAs; D019301:Oleic Acid; D019308:Palmitic Acid; D051057:Proto-Oncogene Proteins c-akt; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
keywords: FFAs; HepG2; NAFLD; NASH; microRNAs