Emerging role for linear and circular spermine oxidase rnas in skeletal muscle physiopathology

Jonathan Fernando Reinoso-Sánchez, Giulia Baroli, Guglielmo Duranti, Silvia Scaricamazza, Stefania Sabatini, Cristiana Valle, Mariangela Morlando, Robert Anthony Casero, Irene Bozzoni, Paolo Mariottini, Roberta Ceci, Manuela Cervelli

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Skeletal muscle atrophy is a pathological condition so far without effective treatment and poorly understood at a molecular level. Emerging evidence suggest a key role for circular RNAs (circRNA) during myogenesis and their deregulation has been reported to be associated with muscle diseases. Spermine oxidase (SMOX), a polyamine catabolic enzyme plays a critical role in muscle differentiation and the existence of a circRNA arising from SMOX gene has been recently identified. In this study, we evaluated the expression profile of circular and linear SMOX in both C2C12 differentiation and dexamethasone-induced myotubes atrophy. To validate our findings in vivo their expression levels were also tested in two murine models of amyotrophic lateral sclerosis: SOD1G93A and hFUS+/+, characterized by progressive muscle atrophy. During C2C12 differentiation, linear and circular SMOX show the same trend of expression. Interestingly, in atrophy circSMOX levels significantly increased compared to the physiological state, in both in vitro and in vivo models. Our study demonstrates that SMOX represents a new player in muscle physiopathology and provides a scientific basis for further investigation on circSMOX RNA as a possible new therapeutic target for the treatment of muscle atrophy.

Original languageEnglish (US)
Article number8227
Pages (from-to)1-19
Number of pages19
JournalInternational journal of molecular sciences
Issue number21
StatePublished - Nov 1 2020


  • Amyotrophic lateral sclerosis murine models
  • CircRNA
  • Skeletal muscle atrophy
  • Spermine oxidase

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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