title: Growth arrest-specific transcript 5 associated snoRNA levels are related to p53 expression and DNA damage in colorectal cancer.
abstract: BACKGROUND
  The growth arrest-specific transcript 5 gene (GAS5) encodes a long noncoding RNA (lncRNA) and hosts a number 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 the potential 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 assess the relationship between p53 and the GAS5 snoRNAs in cancer cell lines and in normal, pre-malignant, and malignant human colorectal tissue and used biological techniques to suggest potential roles for these snoRNAs in the DNA damage response.
  
  
  RESULTS
  GAS5-derived snoRNA expression was induced by DNA damage in a p53-dependent manner in colorectal cancer cell lines and their levels were not affected by DICER. Furthermore, p53 levels strongly correlated with GAS5-derived snoRNA expression in colorectal tissue.
  
  
  CONCLUSIONS
  In aggregate, these data suggest that the GAS5-derived snoRNAs are under control of p53 and that they have an 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 as endogenous controls in qPCR quantifications we show that their use as housekeeping genes in DNA damage experiments can lead to inaccurate results.
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Krell
authors.affiliation: HPB Surgical Unit, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom.
authors.forename: Adam E
authors.initials: AE
authors.lastname: Frampton
authors.affiliation: Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital Campus, London, United Kingdom.
authors.forename: Reza
authors.initials: R
authors.lastname: Mirnezami
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom.
authors.forename: Victoria
authors.initials: V
authors.lastname: Harding
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom.
authors.forename: Alex
authors.initials: A
authors.lastname: De Giorgio
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Roca Alonso
authors.affiliation: Department of Histopathology, Hammersmith Hospital, London, United Kingdom.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Cohen
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ottaviani
authors.affiliation: Institute for Computing Applications "Mauro Picone", National Research Council, Rome, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Colombo
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Jacob
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom.
authors.forename: Loredana
authors.initials: L
authors.lastname: Pellegrino
authors.affiliation: Colorectal Surgical Unit, Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, United Kingdom.
authors.forename: Gordon
authors.initials: G
authors.lastname: Buchanan
authors.affiliation: Department of Oncology, Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, United Kingdom.
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom.
authors.forename: Leandro
authors.initials: L
authors.lastname: Castellano
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D053487:DEAD-box RNA Helicases / Q000235:genetics; D004249:DNA Damage; D004317:Doxorubicin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D020043:Genes, Essential; D045325:HCT116 Cells; D006801:Humans; D062085:RNA, Long Noncoding / Q000235:genetics*; D020537:RNA, Small Nucleolar / Q000235:genetics*; D043244:Ribonuclease III / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C561567:GAS5 long non-coding RNA, human; D062085:RNA, Long Noncoding; D020537:RNA, Small Nucleolar; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases