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

Oncogene. 2009 Jan 15;28(2):195-208. doi: 10.1038/onc.2008.373. Epub 2008 Oct 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Cell Adhesion
  • 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
  • Dexamethasone / pharmacology
  • Down-Regulation
  • Expressed Sequence Tags
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / physiology*
  • RNA, Small Nucleolar / biosynthesis
  • RNA, Small Nucleolar / genetics
  • RNA, Small Nucleolar / physiology*
  • Radiation Tolerance / genetics
  • Thymoma / metabolism
  • Thymoma / pathology
  • Thymus Neoplasms / metabolism
  • Thymus Neoplasms / pathology
  • Tumor Stem Cell Assay
  • Ultraviolet Rays


  • Antineoplastic Agents
  • RNA, Neoplasm
  • RNA, Small Nucleolar
  • growth arrest specific transcript 5
  • Dexamethasone