title: microRNA changes in liver tissue associated with fibrosis progression in patients with hepatitis C.
abstract: OBJECTIVE
  Accumulating evidence indicates that microRNAs play a role in a number of disease processes including the pathogenesis of liver fibrosis in hepatitis C infection. Our goal is to add to the accruing information regarding microRNA deregulation in liver fibrosis to increase our understanding of the underlying mechanisms of pathology and progression.
  
  
  METHODS
  We used next generation sequencing to profile all detectable microRNAs in liver tissue and serum from patients with hepatitis C, stages F1-F4 of fibrosis.
  
  
  RESULTS
  We found altered expression of several microRNAs, in particular, miR-182, miR199a-5p, miR-200a-5p and miR-183 were found to be significantly upregulated in tissue from liver biopsies of hepatitis C patients with advanced fibrosis, stage F3 and F4, when compared with liver biopsies from patients with early fibrosis, stages F1 and F2. We also found miR-148-5p, miR-1260b, miR-122-3p and miR-378i among the microRNAs most significantly down-regulated from early to advanced fibrosis of the liver. We also sequenced the serum microRNAs; however, we were not able to detect significant changes in circulating microRNAs associated with fibrosis stage after adjusting for multiple tests.
  
  
  CONCLUSIONS
  Adding measurements of tissue microRNAs acquired during routine biopsies will continue to increase our knowledge of underlying mechanisms of fibrosis. Our goal is that these data, in combination with studies from other researchers and future long-term studies, could be used to enhance the staging accuracy of liver biopsies and expand the surveillance of patients at increased risk for cancer and progression to advanced fibrosis.
authors.affiliation: Neurogenomics, Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Kendall R
authors.identifier: http://orcid.org/0000-0001-8833-6323
authors.initials: KR
authors.lastname: Van Keuren-Jensen
authors.affiliation: Neurogenomics, Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Ivana
authors.initials: I
authors.lastname: Malenica
authors.affiliation: Neurogenomics, Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Courtright
authors.affiliation: Neurogenomics, Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Layla T
authors.initials: LT
authors.lastname: Ghaffari
authors.affiliation: Neurogenomics, Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Alex P
authors.initials: AP
authors.lastname: Starr
authors.affiliation: Neurogenomics, Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Raghu P
authors.initials: RP
authors.lastname: Metpally
authors.affiliation: Neurogenomics, Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Taylor A
authors.initials: TA
authors.lastname: Beecroft
authors.affiliation: Neurogenomics, Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Elizabeth W J
authors.initials: EW
authors.lastname: Carlson
authors.affiliation: Neurogenomics, Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kiefer
authors.affiliation: Division of Gastroenterology/Hepatology, Scripps, La Jolla, CA, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Pockros
authors.affiliation: Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Rakela
mesh_terms: D000368:Aged; D001706:Biopsy; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000737:chemistry* / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000235:genetics* / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012307:Risk Factors; D017423:Sequence Analysis, RNA; D013997:Time Factors
chemical_list: D005819:Genetic Markers; D035683:MicroRNAs
keywords: fibrosis; hepatitis C; liver; microRNA; sequencing