4.8 Article Retracted Publication

被撤回的出版物: Coordinated Silencing of MYC-Mediated miR-29 by HDAC3 and EZH2 as a Therapeutic Target of Histone Modification in Aggressive B-Cell Lymphomas (Retracted article. See vol. 41, pg. 1198, 2023)

Journal

CANCER CELL
Volume 22, Issue 4, Pages 506-523

Publisher

CELL PRESS
DOI: 10.1016/j.ccr.2012.09.003

Keywords

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Funding

  1. National Cancer Institute [R01 CA137123]
  2. Maher Fund
  3. Susan and John Sykes Lymphoma Research Fund
  4. Lymphoma Research Foundation

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We investigated the transcriptional and epigenetic repression of miR-29 by MYC, HDAC3, and EZH2 in mantle cell lymphoma and other MYC-associated lymphomas. We demonstrate that miR-29 is repressed by MYC through a corepressor complex with HDAC3 and EZH2. MYC contributes to EZH2 upregulation via repression of the EZH2 targeting miR-26a, and EZH2 induces MYC via inhibition of the MYC targeting miR-494 to create positive feedback. Combined inhibition of HDAC3 and EZH2 cooperatively disrupted the MYC-EZH2-miR-29 axis, resulting in restoration of miR-29 expression, downregulation of miR-29-targeted genes, and lymphoma growth suppression in vitro and in vivo. These findings define a MYC-mediated miRNA repression mechanism, shed light on MYC lymphomagenesis mechanisms, and reveal promising therapeutic targets for aggressive B-cell malignancies.

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