Effect of ret/PTC 1 rearrangement 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 nt in length that have been found to control cell growth, differentiation and apoptosis. miRNAs negatively regulate their target genes and recently have been implicated in tumourigenesis. Furthermore, miRNA expression profiling correlates with various cancers, with these genes thought to act as both tumour suppressors and oncogenes. ret/PTC 1 is an oncogene with constitutive kinase activity implicated in the development of papillary thyroid carcinoma (PTC). This rearrangement leads to aberrant MAPK activation that is implicated in PTC tumourigenesis.


OBJECTIVE
The aim of this study was to identify the effect that ret/PTC 1 has on transcription and post-transcriptional regulation in PTC by using DNA microarray and microRNA analysis.


RESULTS
DNA microarray analysis revealed a group of genes differentially expressed between normal thyroid cell lines and those harbouring a ret/PTC 1 rearrangement.Furthermore, a unique miRNA expression signature differentiated between PTC cell lines with ret/PTC 1 and a normal thyroid cell line. 21 miRNAs showed significant overexpression and 14 miRNAs showed underexpression in these cell lines when compared to normal thyroid. Several of these up/down regulated miRNAs may be involved in PTC pathogenesis.
Cahill
Susanne
S
Dept. of Histopathology, University of Dublin, Trinity College, Dublin, Ireland. sucahill@tcd.ie
Smyth
Paul
P
Finn
Stephen P
SP
Denning
Karen
K
Flavin
Richard
R
O'Regan
Esther M
EM
Li
Jinghuan
J
Potratz
Astrid
A
Guenther
Simone M
SM
Henfrey
Richard
R
O'Leary
John J
JJ
Sheils
Orla
O
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015321:Gene Rearrangement; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D014408:Biomarkers, Tumor; D035683:MicroRNAs; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; C093573:ret-PTC fusion oncoproteins, human