title: Changes in microRNA expression during disease progression in patients with chronic viral hepatitis.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) have been involved in hepatocarcinogenesis, but little is known on their role in the progression of chronic viral hepatitis. Aim of this study was to identify miRNA signatures associated with stages of disease progression in patients with chronic viral hepatitis.
  
  
  METHODS
  MiRNA expression profile was investigated in liver biopsies from patients with chronic viral hepatitis and correlated with clinical, virological and histopathological features. Relevant miRNAs were further investigated.
  
  
  RESULTS
  Most of the significant changes in miRNA expression were associated with liver fibrosis stages and included the significant up-regulation of a group of miRNAs that were demonstrated to target the master regulators of epithelial-mesenchymal transition ZEB1 and ZEB2 and involved in the preservation of epithelial cell differentiation, but also in cell proliferation and fibrogenesis. In agreement with miRNA data, immunostaining of liver biopsies showed that expression of the epithelial marker E-cadherin was maintained in severe fibrosis/cirrhosis while expression of ZEBs and other markers of epithelial-mesenchymal transition were low or absent. Severe liver fibrosis was also significantly associated with the down-regulation of miRNAs with antiproliferative and tumour suppressor activity. Similar changes in miRNA and target gene expression were demonstrated along with disease progression in a mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis, suggesting that they might represent a general response to liver injury.
  
  
  CONCLUSIONS
  Chronic viral hepatitis progression is associated with the activation of miRNA pathways that promote cell proliferation and fibrogenesis, but preserve the differentiated hepatocyte phenotype.
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy; IOV Istituto Oncologico Veneto, Padova, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sinigaglia
authors.forename: Enrico
authors.initials: E
authors.lastname: Lavezzo
authors.forename: Marta
authors.initials: M
authors.lastname: Trevisan
authors.forename: Tiziana
authors.initials: T
authors.lastname: Sanavia
authors.forename: Barbara
authors.initials: B
authors.lastname: Di Camillo
authors.forename: Elektra
authors.initials: E
authors.lastname: Peta
authors.forename: Melania
authors.initials: M
authors.lastname: Scarpa
authors.forename: Ignazio
authors.initials: I
authors.lastname: Castagliuolo
authors.forename: Maria
authors.initials: M
authors.lastname: Guido
authors.forename: Samantha
authors.initials: S
authors.lastname: Sarcognato
authors.forename: Rocco
authors.initials: R
authors.lastname: Cappellesso
authors.forename: Ambrogio
authors.initials: A
authors.lastname: Fassina
authors.forename: Romilda
authors.initials: R
authors.lastname: Cardin
authors.forename: Fabio
authors.initials: F
authors.lastname: Farinati
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palù
authors.forename: Luisa
authors.initials: L
authors.lastname: Barzon
mesh_terms: D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000821:virology; D008106:Liver Cirrhosis, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000235:genetics; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D005819:Genetic Markers; D018398:Homeodomain Proteins; D035683:MicroRNAs; D012097:Repressor Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: chronic viral hepatitis; epithelial-mesenchymal transition; liver fibrosis; liver injury; microRNA