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Cancer Cell. 2008 Nov 4;14(5):369-81. doi: 10.1016/j.ccr.2008.10.006.

NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma.

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  • 1Department of Molecular Virology, Human Cancer Genetics Program, The Ohio State University, Columbus, OH 43210, USA.

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-kappaB acting through YY1 and the Polycomb group. During myogenesis, NF-kappaB 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-kappaB-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-kappaB-YY1-miR-29 regulatory circuit whose disruption may contribute to RMS.

PMID:
18977326
PMCID:
PMC3829205
DOI:
10.1016/j.ccr.2008.10.006
[PubMed - indexed for MEDLINE]
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