A molecular pathway for cancer cachexia-induced muscle atrophy revealed at single-nucleus resolution.
Cell Rep
; 43(8): 114587, 2024 Aug 27.
Article
em En
| MEDLINE
| ID: mdl-39116208
ABSTRACT
Cancer cachexia is a prevalent and often fatal wasting condition that cannot be fully reversed with nutritional interventions. Muscle atrophy is a central component of the syndrome, but the mechanisms whereby cancer leads to skeletal muscle atrophy are not well understood. We performed single-nucleus multi-omics on skeletal muscles from a mouse model of cancer cachexia and profiled the molecular changes in cachexic muscle. Our results revealed the activation of a denervation-dependent gene program that upregulates the transcription factor myogenin. Further studies showed that a myogenin-myostatin pathway promotes muscle atrophy in response to cancer cachexia. Short hairpin RNA inhibition of myogenin or inhibition of myostatin through overexpression of its endogenous inhibitor follistatin prevented cancer cachexia-induced muscle atrophy in mice. Our findings uncover a molecular basis of muscle atrophy associated with cancer cachexia and highlight potential therapeutic targets for this disorder.
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Base de dados:
MEDLINE
Assunto principal:
Caquexia
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Atrofia Muscular
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Miogenina
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Miostatina
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article