Muscle-specific E3 ubiquitin ligases are involved in muscle atrophy of cancer cachexia: An in vitro and in vivo study

  • Authors:
    • Lei Yuan
    • Jun Han
    • Qingyang Meng
    • Qiulei Xi
    • Qiulin Zhuang
    • Yi Jiang
    • Yusong Han
    • Bo Zhang
    • Jing Fang
    • Guohao Wu
  • View Affiliations

  • Published online on: March 9, 2015     https://doi.org/10.3892/or.2015.3845
  • Pages: 2261-2268
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Abstract

Muscle atrophy F-Box (MAFbx)/atrogin-1 and muscle ring-finger-1 (MuRF-1) have been identified as two muscle-specific E3 ubiquitin ligases that are highly expressed in skeletal muscle during muscle atrophy. However, the role of muscle-specific E3 ubiquitin ligases during the process of muscle atrophy of cancer cachexia remains largely unknown. In the present study, we analyzed the expression of atrogin-1 and MuRF-1 in the skeletal muscle of patients with malignant and benign disease. The possible mechanisms were studied both in a colon 26-induced cancer cachexia mouse model and in tumor necrosis factor-α (TNF-α) induced atrophy C2C12 cells. Our results demonstrated that atrogin-1 and MuRF-1 tended to be increased in the skeletal muscle of patients with malignant disease even before weight loss. Non-tumor body weights and gastrocnemius weights were significantly decreased while expression levels of ubiquitin proteasome pathway associated genes (atrogin-1, MuRF-1, ubiquitin and E2-14K) were upregulated in cancer cachexia mice. Significant myotube atrophy with atrogin-1 overexpression was observed in the C2C12 cells treated with TNF-α. Meanwhile, knockdown of atrogin-1 by small interfering RNA (siRNA) protected C2C12 cells from the adverse effect of TNF-α. In conclusion, muscle-specific E3 ubiquitin ligases were upregulated during cancer cachexia, and atrogin-1 may be a potential molecular target for treating muscle atrophy induced by cancer cachexia.
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May-2015
Volume 33 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yuan L, Han J, Meng Q, Xi Q, Zhuang Q, Jiang Y, Han Y, Zhang B, Fang J, Wu G, Wu G, et al: Muscle-specific E3 ubiquitin ligases are involved in muscle atrophy of cancer cachexia: An in vitro and in vivo study. Oncol Rep 33: 2261-2268, 2015
APA
Yuan, L., Han, J., Meng, Q., Xi, Q., Zhuang, Q., Jiang, Y. ... Wu, G. (2015). Muscle-specific E3 ubiquitin ligases are involved in muscle atrophy of cancer cachexia: An in vitro and in vivo study. Oncology Reports, 33, 2261-2268. https://doi.org/10.3892/or.2015.3845
MLA
Yuan, L., Han, J., Meng, Q., Xi, Q., Zhuang, Q., Jiang, Y., Han, Y., Zhang, B., Fang, J., Wu, G."Muscle-specific E3 ubiquitin ligases are involved in muscle atrophy of cancer cachexia: An in vitro and in vivo study". Oncology Reports 33.5 (2015): 2261-2268.
Chicago
Yuan, L., Han, J., Meng, Q., Xi, Q., Zhuang, Q., Jiang, Y., Han, Y., Zhang, B., Fang, J., Wu, G."Muscle-specific E3 ubiquitin ligases are involved in muscle atrophy of cancer cachexia: An in vitro and in vivo study". Oncology Reports 33, no. 5 (2015): 2261-2268. https://doi.org/10.3892/or.2015.3845