NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. Cancer Cell 2008 Nov 04;14(5):369-81
Date
11/04/2008Pubmed ID
18977326Pubmed Central ID
PMC3829205DOI
10.1016/j.ccr.2008.10.006Scopus ID
2-s2.0-54549119169 (requires institutional sign-in at Scopus site) 550 CitationsAbstract
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.
Author List
Wang H, Garzon R, Sun H, Ladner KJ, Singh R, Dahlman J, Cheng A, Hall BM, Qualman SJ, Chandler DS, Croce CM, Guttridge DCMESH terms used to index this publication - Major topics in bold
AnimalsBlotting, Western
Cell Cycle
Cell Differentiation
Cell Proliferation
Cells, Cultured
Chromatin Immunoprecipitation
Computational Biology
Down-Regulation
Feedback, Physiological
Fibroblasts
Gene Expression Regulation, Developmental
Humans
Mice
Mice, Inbred C57BL
MicroRNAs
Muscle Development
Myoblasts, Skeletal
NF-kappa B
Nucleic Acid Conformation
Promoter Regions, Genetic
Rhabdomyosarcoma
Signal Transduction
YY1 Transcription Factor