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Published on: February 24, 2026
GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer
M Mourtada-Maarabouni1, M R Pickard, V L Hedge
1Institute for Science and Technology in Medicine and School of Life Sciences, Keele University, Staffordshire, UK.
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.
Insights
Growth arrest-specific transcript 5 (GAS5) regulates cell survival and proliferation, impacting cancer development. Reduced GAS5 levels in breast cancer suggest its role as a tumor suppressor gene, potentially through encoded small nucleolar RNAs (snoRNAs).
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Effective control of cell survival and proliferation is crucial for preventing oncogenesis and for successful cancer therapy.
- Growth arrest-specific transcript 5 (GAS5) has been identified as a key regulator of mammalian apoptosis and cell population growth.
Purpose of the Study:
- To investigate the role of GAS5 in controlling cell survival, proliferation, and its implications in breast cancer.
- To explore the potential tumor suppressor function of GAS5 and its encoded small nucleolar RNAs (snoRNAs).
Main Methods:
- Functional expression cloning was employed to identify GAS5.
- Analysis of GAS5 transcript processing, apoptosis induction, and expression levels in breast cancer tissues.
- Investigation of the protein-coding potential of GAS5 and its intronic snoRNA products.
Main Results:
- GAS5 transcripts play a critical role in regulating mammalian apoptosis and cell population growth.
- GAS5 expression can induce growth arrest and apoptosis independently of other stimuli in certain cell lines.
- GAS5 transcript levels are significantly reduced in breast cancer samples compared to normal adjacent tissues.
Conclusions:
- GAS5, through its encoded snoRNAs, represents a novel class of tumor suppressor genes involved in oncogenesis.
- GAS5's regulation of apoptosis and proliferation suggests its potential as a therapeutic target in cancer treatment.
- The findings highlight the importance of snoRNAs in controlling cancer development and therapy sensitivity.
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