Open Access Research

Effect of BRAFV600E mutation on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model

Susanne Cahill1, Paul Smyth1, Karen Denning1, Richard Flavin1, Jinghuan Li1, Astrid Potratz2, Simone M Guenther2, Richard Henfrey2, John J O'Leary1 and Orla Sheils1*

Author Affiliations

1 Dept. of Histopathology, University of Dublin, Trinity College, Dublin, Ireland

2 Applied Biosystems, Foster City, CA, USA

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Molecular Cancer 2007, 6:21  doi:10.1186/1476-4598-6-21

Published: 13 March 2007

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.

Aim

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.