Author/Authors :
Zhang، نويسنده , , Xinwei and Zhao، نويسنده , , Xiaohong and Fiskus، نويسنده , , Warren and Lin، نويسنده , , Jianhong and Lwin، نويسنده , , Tint and Rao، نويسنده , , Rekha and Zhang، نويسنده , , Yizhuo and Chan، نويسنده , , John C. and Fu، نويسنده , , Kai and Marquez، نويسنده , , Victor E. and Chen-Kiang، نويسنده , , Selina and Moscinski، نويسنده , , Lynn C. and Seto، نويسنده , , Edward and Dalton، نويسنده , , William S. and Wright، نويسنده , , Kenneth L. and Sotomayor، نويسنده , , Eduardo and Bhalla، نويسنده , , Kapil and Tao، نويسنده , , Jianguo، نويسنده ,
Abstract :
Summary
estigated 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.
