title: The miR-200 family is increased in dysplastic lesions in ulcerative colitis patients.
abstract: BACKGROUND
  Colorectal cancer (CRC) is a life-threatening complication of ulcerative colitis (UC), and patients are routinely screened for the development of precancerous lesions (dysplasia). However, rates of CRC development in patients with confirmed low-grade dysplasia vary widely between studies, suggesting a large degree of heterogeneity between these lesions that is not detectable macroscopically. A better understanding of the underlying molecular changes that occur in dysplasia will help to identify lesions at higher risk of malignancy. MicroRNAs (miRNAs) post-transcriptionally regulate protein expression and cell-signalling networks. Aberrant miRNA expression is a feature of sporadic CRC but much less is known about the changes that occur in dysplasia and in UC.
  
  
  METHODS
  Comprehensive microRNA profiling was performed on RNA extracted from UC dysplastic lesions (n = 7) and UC controls (n = 10). The expression of miRNAs in UC post inflammatory polyps (n = 7) was also assessed. Candidate miRNAs were further validated by qPCR, and miRNA in situ hybridization. Serum levels of miRNAs were also assessed with a view to identification of non-invasive biomarkers of dysplasia.
  
  
  RESULTS
  UC dysplasia was associated with a shift in miRNA expression profiles that was not seen in inflammatory polyps. In particular, levels of miR-200b-3p were increased in dysplasia, and this miRNA was localised to epithelial cells in dysplastic lesions and in UC cancers. No changes in miRNA levels were detected in the serum.
  
  
  CONCLUSIONS
  UC-Dysplasia is linked to altered miRNA expression in the mucosa and elevated miR-200b-3p levels.
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine & Dentistry, London E1 2AT United Kingdom.
authors.forename: Amy
authors.initials: A
authors.lastname: Lewis
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine & Dentistry, London E1 2AT United Kingdom.|IBD Unit, Complesso Integrato Columbus, Gemelli Hospital Catholic University Foundation, Rome, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Felice
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine & Dentistry, London E1 2AT United Kingdom.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kumagai
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine & Dentistry, London E1 2AT United Kingdom.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lai
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine & Dentistry, London E1 2AT United Kingdom.
authors.forename: Kriti
authors.initials: K
authors.lastname: Singh
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine & Dentistry, London E1 2AT United Kingdom.
authors.forename: Rosemary R
authors.initials: RR
authors.lastname: Jeffery
authors.affiliation: Department of Histopathology, The Royal London Hospital, London, E1 1BB United Kingdom.
authors.forename: Roger
authors.initials: R
authors.lastname: Feakins
authors.affiliation: Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.|The University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Eleni
authors.initials: E
authors.lastname: Giannoulatou
authors.affiliation: IBD Unit, Complesso Integrato Columbus, Gemelli Hospital Catholic University Foundation, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Armuzzi
authors.affiliation: Barts Cancer Institute, Barts and The London School of Medicine & Dentistry, London EC1M 6BQ United Kingdom.
authors.forename: Noor
authors.initials: N
authors.lastname: Jawad
authors.affiliation: Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine & Dentistry, London E1 2AT United Kingdom.
authors.forename: James O
authors.initials: JO
authors.lastname: Lindsay
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine & Dentistry, London E1 2AT United Kingdom.
authors.forename: Andrew
authors.identifier: http://orcid.org/0000-0002-8263-5733
authors.initials: A
authors.lastname: Silver
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000473:pathology*; D003111:Colonic Polyps / Q000235:genetics / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results
chemical_list: D005819:Genetic Markers; C533896:MIRN200 microRNA, human; D035683:MicroRNAs