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Macquarrie KL, Yao Z, Young JM, et al. miR-206 integrates multiple components of differentiation pathways to control the transition from growth to differentiation in rhabdomyosarcoma cells. Skelet Muscle. 2012;2(1):7doi: 10.1186/2044-5040-2-7.
Macquarrie, K. L., Yao, Z., Young, J. M., Cao, Y., & Tapscott, S. J. (2012). miR-206 integrates multiple components of differentiation pathways to control the transition from growth to differentiation in rhabdomyosarcoma cells. Skeletal muscle, 2(1), 7. https://doi.org/10.1186/2044-5040-2-7
Macquarrie, Kyle L, et al. "miR-206 integrates multiple components of differentiation pathways to control the transition from growth to differentiation in rhabdomyosarcoma cells." Skeletal muscle vol. 2,1 (2012): 7. doi: https://doi.org/10.1186/2044-5040-2-7
Macquarrie KL, Yao Z, Young JM, Cao Y, Tapscott SJ. miR-206 integrates multiple components of differentiation pathways to control the transition from growth to differentiation in rhabdomyosarcoma cells. Skelet Muscle. 2012 Apr 29;2(1):7. doi: 10.1186/2044-5040-2-7. PMID: 22541669; PMCID: PMC3417070.
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Skelet Muscle. 2012 Apr 29;2(1):7. doi: 10.1186/2044-5040-2-7.

miR-206 integrates multiple components of differentiation pathways to control the transition from growth to differentiation in rhabdomyosarcoma cells.

Skeletal muscle

Kyle L Macquarrie, Zizhen Yao, Janet M Young, Yi Cao, Stephen J Tapscott

Affiliations

  1. Human Biology Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, C3-168, Seattle, WA, 98109, USA. [email protected].

PMID: 22541669 PMCID: PMC3417070 DOI: 10.1186/2044-5040-2-7

Abstract

BACKGROUND: Similar to replicating myoblasts, many rhabdomyosarcoma cells express the myogenic determination gene MyoD. In contrast to myoblasts, rhabdomyosarcoma cells do not make the transition from a regulative growth phase to terminal differentiation. Previously we demonstrated that the forced expression of MyoD with its E-protein dimerization partner was sufficient to induce differentiation and suppress multiple growth-promoting genes, suggesting that the dimer was targeting a switch that regulated the transition from growth to differentiation. Our data also suggested that a balance between various inhibitory transcription factors and MyoD activity kept rhabdomyosarcomas trapped in a proliferative state.

METHODS: Potential myogenic co-factors were tested for their ability to drive differentiation in rhabdomyosarcoma cell culture models, and their relation to MyoD activity determined through molecular biological experiments.

RESULTS: Modulation of the transcription factors RUNX1 and ZNF238 can induce differentiation in rhabdomyosarcoma cells and their activity is integrated, at least in part, through the activation of miR-206, which acts as a genetic switch to transition the cell from a proliferative growth phase to differentiation. The inhibitory transcription factor MSC also plays a role in controlling miR-206, appearing to function by occluding a binding site for MyoD in the miR-206 promoter.

CONCLUSIONS: These findings support a network model composed of coupled regulatory circuits with miR-206 functioning as a switch regulating the transition from one stable state (growth) to another (differentiation).

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