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Effect of RNA oligonucleotide targeting Foxo-1 on muscle growth in normal and cancer cachexia mice

Cancer Gene Therapy volume 14, pages 945952 (2007) | Download Citation

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Abstract

Foxo-1, a member of the Foxo forkhead type transcription factors, is markedly upregulated in skeletal muscle in energy-deprived states such as fasting, cancer and severe diabetes. In this study, we target the Foxo-1 mRNA in a mouse skeletal myoblast cell line C2C12 and in vivo models of normal and cancer cachexia mice by a Foxo-1 specific RNA oligonucleotide. Our results demonstrate that the RNA oligonucleotide can reduce the expression of Foxo-1 in cells and in normal and cachectic mice, leading to an increase in skeletal muscle mass of the mice. In search for the possible downstream target genes of Foxo-1, we show that when Foxo-1 expression is blocked both in cells and in mice, the level of MyoD, a myogenic factor, is increased while a muscle negative regulator GDF-8 or myostatin is suppressed. Taken together, these results show that Foxo-1 pays a critical role in development of muscle atrophy, and suggest that Foxo-1 is a potential molecular target for treatment of muscle wasting conditions.

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Author information

Author notes

    • C-M Liu
    •  & Z Yang

    These two authors contributed equally.

Affiliations

  1. Molecular Virology Research Center, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China

    • C-M Liu
    • , Z Yang
    • , C-W Liu
    • , R Wang
    •  & P Tien
  2. Oligos Etc. Inc., Wilsonville, OR, USA

    • R Dale
    •  & L-Q Sun

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Correspondence to P Tien or L-Q Sun.

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DOI

https://doi.org/10.1038/sj.cgt.7701091

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