NF-κB-YY1-miR-29 Regulatory Circuitry in Skeletal Myogenesis and Rhabdomyosarcoma

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Abstract

Studies support the importance of microRNAs in physiological and pathological processes. Here we describe the regulation and function of miR-29 in myogenesis and rhabdomyosarcoma (RMS). Results demonstrate that in myoblasts, miR-29 is repressed by NF-κB acting through YY1 and the Polycomb group. During myogenesis, NF-κB and YY1 downregulation causes derepression of miR-29, which in turn accelerates differentiation by targeting its repressor YY1. However, in RMS cells and primary tumors that possess impaired differentiation, miR-29 is epigenetically silenced by an activated NF-κB-YY1 pathway. Reconstitution of miR-29 in RMS in mice inhibits tumor growth and stimulates differentiation, suggesting that miR-29 acts as a tumor suppressor through its promyogenic function. Together, these results identify a NF-κB-YY1-miR-29 regulatory circuit whose disruption may contribute to RMS. © 2008 Elsevier Inc. All rights reserved.

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Wang, H., Garzon, R., Sun, H., Ladner, K. J., Singh, R., Dahlman, J., … Guttridge, D. C. (2008). NF-κB-YY1-miR-29 Regulatory Circuitry in Skeletal Myogenesis and Rhabdomyosarcoma. Cancer Cell, 14(5), 369–381. https://doi.org/10.1016/j.ccr.2008.10.006

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