Abstract:
: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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Zhang X,Zhao X,Fiskus W,Lin J,Lwin T,Rao R,Zhang Y,Chan JC,Fu K,Marquez VE,Chen-Kiang S,Moscinski LC,Seto E,Dalton WS,Wright KL,Sotomayor E,Bhalla K,Tao Jdoi
10.1016/j.ccr.2012.09.003subject
Has Abstractpub_date
2012-10-16 00:00:00pages
506-523issue
4eissn
1535-6108issn
1878-3686journal_volume
22pub_type
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