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@article{Krell:2014:10.1371/journal.pone.0098561,
author = {Krell, J and Frampton, AE and Mirnezami, R and Harding, V and De, Giorgio A and Alonso, LR and Cohen, P and Ottaviani, S and Colombo, T and Jacob, J and Pellegrino, L and Buchanan, G and Stebbing, J and Castellano, L},
doi = {10.1371/journal.pone.0098561},
journal = {PLOS One},
title = {Growth Arrest-Specific Transcript 5 Associated snoRNA Levels Are Related to p53 Expression and DNA Damage in Colorectal Cancer},
url = {http://dx.doi.org/10.1371/journal.pone.0098561},
volume = {9},
year = {2014}
}

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TY  - JOUR
AB  - Background: The growth arrest-specific transcript 5 gene (GAS5) encodes a long noncoding RNA (lncRNA) and hosts anumber of small nucleolar RNAs (snoRNAs) that have recently been implicated in multiple cellular processes and cancer.Here, we investigate the relationship between DNA damage, p53, and the GAS5 snoRNAs to gain further insight into thepotential role of this locus in cell survival and oncogenesis both in vivo and in vitro.Methods: We used quantitative techniques to analyse the effect of DNA damage on GAS5 snoRNA expression and to assessthe relationship between p53 and the GAS5 snoRNAs in cancer cell lines and in normal, pre-malignant, and malignanthuman colorectal tissue and used biological techniques to suggest potential roles for these snoRNAs in the DNA damageresponse.Results: GAS5-derived snoRNA expression was induced by DNA damage in a p53-dependent manner in colorectal cancercell lines and their levels were not affected by DICER. Furthermore, p53 levels strongly correlated with GAS5-derived snoRNAexpression in colorectal tissue.Conclusions: In aggregate, these data suggest that the GAS5-derived snoRNAs are under control of p53 and that they havean important role in mediating the p53 response to DNA damage, which may not relate to their function in the ribosome.We suggest that these snoRNAs are not processed by DICER to form smaller snoRNA-derived RNAs with microRNA (miRNA)-like functions, but their precise role requires further evaluation. Furthermore, since GAS5 host snoRNAs are often used asendogenous controls in qPCR quantifications we show that their use as housekeeping genes in DNA damage experimentscan lead to inaccurate results.
AU  - Krell,J
AU  - Frampton,AE
AU  - Mirnezami,R
AU  - Harding,V
AU  - De,Giorgio A
AU  - Alonso,LR
AU  - Cohen,P
AU  - Ottaviani,S
AU  - Colombo,T
AU  - Jacob,J
AU  - Pellegrino,L
AU  - Buchanan,G
AU  - Stebbing,J
AU  - Castellano,L
DO  - 10.1371/journal.pone.0098561
PY  - 2014///
SN  - 1932-6203
TI  - Growth Arrest-Specific Transcript 5 Associated snoRNA Levels Are Related to p53 Expression and DNA Damage in Colorectal Cancer
T2  - PLOS One
UR  - http://dx.doi.org/10.1371/journal.pone.0098561
UR  - http://hdl.handle.net/10044/1/29188
VL  - 9
ER  -

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