title: Effect of BRAFV600E mutation on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model.
abstract: BACKGROUND
  microRNAs (miRNAs) are a group of non-coding single stranded RNAs measuring approximately 22 nucleotides in length that have been found to control cell growth, differentiation and apoptosis. They negatively regulate target genes and have recently been implicated in tumourigenesis. Furthermore, miRNA expression profiling correlates with various cancers, with these genes thought to act as both tumour suppressors and oncogenes. Recently, a point mutation in the BRAF gene leading to a V600E substitution has been identified as the most common genetic change in papillary thyroid carcinoma (PTC) occurring in 29-69% of cases. This mutation leads to aberrant MAPK activation that is implicated in tumourigenesis.
  
  
  OBJECTIVE
  The aim of this study was to identify the effect that BRAF oncogene has on post-transcriptional regulation in PTC by using microRNA analysis.
  
  
  RESULTS
  A unique miRNA expression signature differentiated between PTC cell lines with BRAF mutations and a normal thyroid cell line. 15 miRNAs were found to be upregulated and 23 miRNAs were downregulated. Several of these up/down regulated miRNAs may be involved in PTC pathogenesis. miRNA profiling will assist in the elucidation of disease pathogenesis and identification biomarkers and targets.
authors.affiliation: Dept. of Histopathology, University of Dublin, Trinity College, Dublin, Ireland. sucahill@tcd.ie
authors.forename: Susanne
authors.initials: S
authors.lastname: Cahill
authors.forename: Paul
authors.initials: P
authors.lastname: Smyth
authors.forename: Karen
authors.initials: K
authors.lastname: Denning
authors.forename: Richard
authors.initials: R
authors.lastname: Flavin
authors.forename: Jinghuan
authors.initials: J
authors.lastname: Li
authors.forename: Astrid
authors.initials: A
authors.lastname: Potratz
authors.forename: Simone M
authors.initials: SM
authors.lastname: Guenther
authors.forename: Richard
authors.initials: R
authors.lastname: Henfrey
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Leary
authors.forename: Orla
authors.initials: O
authors.lastname: Sheils
mesh_terms: D000328:Adult; D002291:Carcinoma, Papillary / Q000235:genetics*; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005973:Glutamine / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics*; D014158:Transcription, Genetic; D014633:Valine / Q000235:genetics
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D005973:Glutamine; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D014633:Valine