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

Susanne Cahill,Jinghuan Li,Karen Denning,Richard Flavin,Paul Smyth,Richard Henfrey,John J O'Leary,Astrid Potratz,Orla Sheils,Simone M Guenther

doi:10.1186/1476-4598-6-21

Susanne Cahill, Jinghuan Li + Show 8 more

Open Access

https://doi.org/10.1186/1476-4598-6-21

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Journal: Molecular Cancer	Publication Date: Mar 13, 2007
Citations: 90	License type: cc-by

Affiliation: Trinity College Dublin

Abstract

BackgroundmicroRNAs (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.AimThe aim of this study was to identify the effect that BRAF oncogene has on post-transcriptional regulation in PTC by using microRNA analysis.ResultsA 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.

Highlights

MicroRNAs 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
papillary thyroid carcinoma (PTC) is defined by several alterations which cause abnormal activation of the mitogen-activated protein kinase (MAPK) pathway, the most prevalent being point mutations in the intracellular signalling kinase BRAF [1,2]
Several recent studies on the regulatory functions of miRNAs suggest that they play critical roles in central processes such as development, cell proliferation and differentiation, stress resistance, metabolism and apoptosis all of which are involved in tumourigenesis [13,15]

Summary

Introduction

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. The recent discovery that a large group of non-coding RNAs called microRNAs (miRNAs) may potentially play a role in cancer has led to a proliferation of miRNA related research of late including the publication of several key reviews [8,9,10,11,12]. Differential expression of miRNAs between malignant tissue and normal tissue and between different types of tumour, has been shown in several key studies, indicating that miRNAs are determinants of clinical diagnostic and prognostic significance [21,22]

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