Pickard, MR, Mourtada-Maarabouni, M and Williams, GT (2013) Long non-coding RNA GAS5 regulates apoptosis in prostate cancer cell lines. Biochim Biophys Acta, 1832 (10). 1613 - 1623. ISSN 0006-3002

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Abstract

While the role of small non-coding RNAs, such as miRNAs, in apoptosis control is well established, long non-coding RNAs (lncRNAs) have received less attention. Growth Arrest-Specific 5 (GAS5) encodes multiple snoRNAs within its introns, while exonic sequences produce lncRNA which can act as a riborepressor of the glucocorticoid and related receptors. GAS5 negatively regulates the survival of lymphoid and breast cells, and is aberrantly expressed in several cancers. Although cellular GAS5 levels decline as prostate cancer cells acquire castration-resistance, the influence of GAS5 on prostate cell survival has not been determined. To address this question, prostate cell lines were transfected with GAS5-encoding plasmids or GAS5 siRNAs, and cell survival was assessed. Basal apoptosis increased, and cell survival decreased, after transfection of 22Rv1 cells with plasmids encoding GAS5 transcripts, including mature GAS5 lncRNA. Similar effects were observed in PC-3 cells. In stable clones of 22Rv1, cell death correlated strongly with cellular GAS5 levels. Induction of 22Rv1 cell death by UV-C irradiation and chemotherapeutic drugs was augmented in cells transiently transfected with GAS5 constructs, and attenuated following down-regulation of GAS5 expression. Again, in these experiments, cell death was strongly correlated with cellular GAS5 levels. Thus, GAS5 promotes the apoptosis of prostate cells, and exonic sequence, i.e. GAS5 lncRNA, is sufficient to mediate this activity. Abnormally low levels of GAS5 expression may therefore reduce the effectiveness of chemotherapeutic agents. Although several lncRNAs have recently been shown to control cell survival, this is the first report of a death-promoting lncRNA in prostate cells.

Item Type: Article
Additional Information: The published version of this article can be accessed online at: https://www.sciencedirect.com/science/article/pii/S0925443913001592?via%3Dihub
Uncontrolled Keywords: lncRNA; GAS5; Prostate; Cancer; Apoptosis; Drug resistance
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Related URLs:
Depositing User: Symplectic
Date Deposited: 26 Jun 2018 07:53
Last Modified: 26 Jun 2018 07:53
URI: http://eprints.keele.ac.uk/id/eprint/5060

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