[PDF][PDF] NF-κB–YY1–miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma

H Wang, R Garzon, H Sun, KJ Ladner, R Singh… - Cancer cell, 2008 - cell.com
H Wang, R Garzon, H Sun, KJ Ladner, R Singh, J Dahlman, A Cheng, BM Hall, SJ Qualman…
Cancer cell, 2008cell.com
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 …
Summary
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.
cell.com