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Growth arrest-specific transcript 5 associated snoRNA levels are related to p53 expression and DNA damage in colorectal cancer
journal contribution
posted on 2023-06-20, 14:17 authored by Jonathan Krell, Adam E Frampton, Reza Mirnezami, Victoria Harding, Alex De Giorgio, Laura Roca Alonso, Patrizia Cohen, Silvia Ottaviani, Teresa Colombo, Jimmy Jacob, Loredana Pellegrino, Gordon Buchanan, Justin Stebbing, Leandro CastellanoLeandro CastellanoBACKGROUND 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.
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Publication status
- Published
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- Published version
Journal
PLoS ONEISSN
1932-6203Publisher
Public Library of ScienceExternal DOI
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6Volume
9Article number
e98561Department affiliated with
- Biochemistry Publications
Full text available
- Yes
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- Yes
Legacy Posted Date
2018-06-15First Open Access (FOA) Date
2018-06-15First Compliant Deposit (FCD) Date
2018-06-15Usage metrics
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