Depletion of HuR in murine skeletal muscle enhances exercise endurance and prevents cancer-induced muscle atrophy


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Janice Sánchez, B., Tremblay, A. M. K., Leduc-Gaudet, J. P., Hall, D. T., Kovacs, E., Ma, J. F., Mubaid, S., Hallauer, P. L., Phillips, B. L., Vest, K. E., Corbett, A. H., Kontoyiannis, D. L., Hussain, S. N. A., Hastings, K. E. M., Di Marco, S. et Gallouzi, I. E. (2019). Depletion of HuR in murine skeletal muscle enhances exercise endurance and prevents cancer-induced muscle atrophy. Nature Communications, 10 (1). Article 4171. ISSN 2041-1723 DOI 10.1038/s41467-019-12186-6

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The master posttranscriptional regulator HuR promotes muscle fiber formation in cultured muscle cells. However, its impact on muscle physiology and function in vivo is still unclear. Here, we show that muscle-specific HuR knockout (muHuR-KO) mice have high exercise endurance that is associated with enhanced oxygen consumption and carbon dioxide production. muHuR-KO mice exhibit a significant increase in the proportion of oxidative type I fibers in several skeletal muscles. HuR mediates these effects by collaborating with the mRNA decay factor KSRP to destabilize the PGC-1α mRNA. The type I fiber-enriched phenotype of muHuR-KO mice protects against cancer cachexia-induced muscle loss. Therefore, our study uncovers that under normal conditions HuR modulates muscle fiber type specification by promoting the formation of glycolytic type II fibers. We also provide a proof-of-principle that HuR expression can be targeted therapeutically in skeletal muscles to combat cancer-induced muscle wasting. © 2019, The Author(s).

Type de document: Article
Mots-clés libres: Alpha tropomyosin Carbon dioxide CD36 antigen Cell nucleus DNA ELAV like protein 1 Hexokinase High mobility group B1 protein Long chain acyl coenzyme A dehydrogenase Low density lipoprotein Messenger RNA Mitochondrial DNA Mitochondrial transcription factor A MyoD protein Myosin heavy chain Myosin heavy chain beta Nuclear respiratory factor 1 Nucleophosmin Peroxisome proliferator activated receptor alpha Peroxisome proliferator activated receptor delta Peroxisome proliferator activated receptor gamma coactivator 1alpha Protein p53 Reduced nicotinamide adenine dinucleotide dehydrogenase (Ubiquinone) Transcription factor Nrf2 Transcription factor Six1 Troponin I Tubulin Tumor necrosis factor receptor superfamily member 6 Uncoupling protein 2 Uncoupling protein 3 Unindexed drug Elavl1 protein, mouse Cancer Cell component Gene expression Induced response Muscle Protein RNA Skeleton Animal cell Animal experiment Animal model Animal tissue Article Cachexia Calorimetry Controlled study DNA extraction Endurance training Energy balance Gene control Gene knockout Genetic transfection Genotype Genotyping technique Grid test Grip strength test Immunoblotting Immunohistochemistry Immunoprecipitation Lewis carcinoma Lung gas exchange Male Malignant neoplasm Mouse mRNA expression level Muscle atrophy Muscle contraction Nonhuman Oxygen consumption Phenotype Polymerase chain reaction Protein depletion Protein expression Real time reverse transcription polymerase chain reaction RNA isolation Rotarod test Skeletal muscle Western blotting Animal Cell line Complication Cross-sectional study Gene expression regulation Genetics Knockout mouse Metabolism Neoplasm Physiology Tumor cell line Murinae Mus Animals Cell Line, Tumor Cross-Sectional Studies ELAV-Like Protein 1 Mice Mice, Knockout Muscle, Skeletal Muscular Atrophy Neoplasms
Date de dépôt: 10 juill. 2023 16:26
Dernière modification: 10 juill. 2023 16:26
Version du document déposé: Version officielle de l'éditeur

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