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GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer

Oncogene volume 28, pages 195–208 (2009)Cite this article

Abstract

Effective control of both cell survival and cell proliferation is critical to the prevention of oncogenesis and to successful cancer therapy. Using functional expression cloning, we have identified GAS5 (growth arrest-specific transcript 5) as critical to the control of mammalian apoptosis and cell population growth. GAS5 transcripts are subject to complex post-transcriptional processing and some, but not all, GAS5 transcripts sensitize mammalian cells to apoptosis inducers. We have found that, in some cell lines, GAS5 expression induces growth arrest and apoptosis independently of other stimuli. GAS5 transcript levels were significantly reduced in breast cancer samples relative to adjacent unaffected normal breast epithelial tissues. The GAS5 gene has no significant protein-coding potential but expression encodes small nucleolar RNAs (snoRNAs) in its introns. Taken together with the recent demonstration of tumor suppressor characteristics in the related snoRNA U50, our observations suggest that such snoRNAs form a novel family of genes controlling oncogenesis and sensitivity to therapy in cancer.

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Acknowledgements

We thank Ms Ria Kishen, Dr Helen Kalirai and Professor Philip Rudland of the Liverpool Cancer Tissue Bank Research Centre for breast cancer and normal breast epithelial RNA samples, Professor Norman Maitland for PNT2C2 and P4E6 cells, and the Wellcome Trust, Breast Cancer Campaign, Leukemia Research Fund and BBSRC for financial support.

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  1. Institute for Science and Technology in Medicine and School of Life Sciences, Keele University, Keele, Staffordshire, UK

    M Mourtada-Maarabouni, M R Pickard, V L Hedge & G T Williams

  2. Department of Haematological Medicine, King's College London, The Rayne Institute, London, UK

    F Farzaneh

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  1. M Mourtada-Maarabouni
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  2. M R Pickard
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  3. V L Hedge
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Correspondence to M Mourtada-Maarabouni or G T Williams.

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Mourtada-Maarabouni, M., Pickard, M., Hedge, V. et al. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene 28, 195–208 (2009). https://doi.org/10.1038/onc.2008.373

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