Effect of BRAFV600E mutation on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model.
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.
Cahill
Susanne
S
Dept. of Histopathology, University of Dublin, Trinity College, Dublin, Ireland. sucahill@tcd.ie
Smyth
Paul
P
Denning
Karen
K
Flavin
Richard
R
Li
Jinghuan
J
Potratz
Astrid
A
Guenther
Simone M
SM
Henfrey
Richard
R
O'Leary
John J
JJ
Sheils
Orla
O
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
D035683:MicroRNAs; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D005973:Glutamine; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D014633:Valine