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

• Published in: Oncogene Vol. 28; no. 2; pp. 195 - 208
• Main Authors: Mourtada-Maarabouni, M, Pickard, M R, Hedge, V L, Farzaneh, F, Williams, G T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15-01-2009; Nature Publishing Group
• Subjects: Animals; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis - radiation effects; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carcinoma, Ductal, Breast - genetics; Carcinoma, Ductal, Breast - metabolism; Carcinoma, Ductal, Breast - pathology; Care and treatment; Cell Adhesion; Cell Biology; Cell growth; Cell Line - drug effects; Cell Line - metabolism; Cell Line - radiation effects; Cell Line, Tumor - drug effects; Cell Line, Tumor - metabolism; Cell Line, Tumor - radiation effects; Control; Dexamethasone - pharmacology; Down-Regulation; Drug resistance; Expressed Sequence Tags; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Human Genetics; Humans; Internal Medicine; Medicine; Medicine & Public Health; Mice; Oncology; original-article; Physiological aspects; Radiation Tolerance - genetics; RNA; RNA, Neoplasm - biosynthesis; RNA, Neoplasm - genetics; RNA, Neoplasm - physiology; RNA, Small Nucleolar - biosynthesis; RNA, Small Nucleolar - genetics; RNA, Small Nucleolar - physiology; Thymoma - metabolism; Thymoma - pathology; Thymus Neoplasms - metabolism; Thymus Neoplasms - pathology; Tumor Stem Cell Assay; Ultraviolet Rays; United Kingdom; growth arrest; apoptosis; breast cancer; drug resistance; snoRNA; oncogenesis
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2008.373

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.