TY - JOUR
T1 - Emerging role for linear and circular spermine oxidase rnas in skeletal muscle physiopathology
AU - Reinoso-Sánchez, Jonathan Fernando
AU - Baroli, Giulia
AU - Duranti, Guglielmo
AU - Scaricamazza, Silvia
AU - Sabatini, Stefania
AU - Valle, Cristiana
AU - Morlando, Mariangela
AU - Casero, Robert Anthony
AU - Bozzoni, Irene
AU - Mariottini, Paolo
AU - Ceci, Roberta
AU - Cervelli, Manuela
N1 - Funding Information:
This work was supported by the Grant to Department of Science, Roma Tre University (MIUR-Italy Dipartimento di Eccellenza, ARTICOLO 1, COMMI 314—337 LEGGE 232/2016) and by the Research project of basic and technological research approved in the Protocols of Scientific and Technological Bilateral Cooperation funded by the Ministry of Health, Italy-United States of America. 2019 “Whole transcriptome analysis in models of extended healthy life-span after spermidine treatment”—MAE0067342. This work was also supported by research grants from the University of Rome ‘Foro Italico’ (“Effects of spermine oxidase (SMOX) overexpression in skeletal muscle physiology and in pathological conditions.”-CDR2.BANDO2017SS) and from the University of Pennsylvania Orphan Disease Center in partnership with the Snyder-Robinson Foundation MDBR-20-135-SRS (RAC) and from ERC-2019-SyG (855923-ASTRA) and AIRC (IG 2019 Id. 23053).
Funding Information:
Funding: This work was supported by the Grant to Department of Science, Roma Tre University (MIUR-Italy Dipartimento di Eccellenza, ARTICOLO 1, COMMI 314—337 LEGGE 232/2016) and by the Research project of basic and technological research approved in the Protocols of Scientific and Technological Bilateral Cooperation funded by the Ministry of Health, Italy-United States of America. 2019 “Whole transcriptome analysis in models of extended healthy life-span after spermidine treatment”—MAE0067342. This work was also supported by research grants from the University of Rome ‘Foro Italico’ (“Effects of spermine oxidase (SMOX) overexpression in skeletal muscle physiology and in pathological conditions.”-CDR2.BANDO2017SS) and from the University of Pennsylvania Orphan Disease Center in partnership with the Snyder-Robinson Foundation MDBR-20-135-SRS (RAC) and from ERC-2019-SyG (855923-ASTRA) and AIRC (IG 2019 Id. 23053).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
KW - Amyotrophic lateral sclerosis murine models
KW - CircRNA
KW - Skeletal muscle atrophy
KW - Spermine oxidase
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U2 - 10.3390/ijms21218227
DO - 10.3390/ijms21218227
M3 - Article
C2 - 33153123
AN - SCOPUS:85095722097
SN - 1661-6596
VL - 21
SP - 1
EP - 19
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 21
M1 - 8227
ER -