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Myc Enforces Overexpression ofEZH2in Early Prostatic Neoplasia via Transcriptional and Post-transcriptional Mechanisms

Overview of attention for article published in Oncotarget, September 2011
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Title
Myc Enforces Overexpression ofEZH2in Early Prostatic Neoplasia via Transcriptional and Post-transcriptional Mechanisms
Published in
Oncotarget, September 2011
DOI 10.18632/oncotarget.327
Pubmed ID
Authors

Cheryl M. Koh, Tsuyoshi Iwata, Qizhi Zheng, Carlise Bethel, Srinivasan Yegnasubramanian, Angelo M. De Marzo

Abstract

EZH2 is part of the PRC2 polycomb repressive complex that is overexpressed in multiple cancer types and has been implicated in prostate cancer initiation and progression. Here, we identify EZH2 as a target of the MYC oncogene in prostate cancer and show that MYC coordinately regulates EZH2 through transcriptional and post-transcriptional means. Although prior studies in prostate cancer have revealed a number of possible mechanisms of EZH2 upregulation, these changes cannot account for the overexpression EZH2 in many primary prostate cancers, nor in most cases of high grade PIN. We report that upregulation of Myc in the mouse prostate results in overexpression of EZH2 mRNA and protein which coincides with reductions in miR-26a and miR-26b, known regulators of EZH2 in some non-prostate cell types, albeit not in others. Further, in human prostate cancer cells, Myc negatively regulates miR-26a and miR-26b via direct binding to their parental Pol II gene promoters, and forced overexpression of miR-26a and miR-26b in prostate cancer cells results in decreased EZH2 levels and suppressed proliferation. In human clinical samples, miR-26a and miR-26b are downregulated in most primary prostate cancers. As a separate mechanism of EZH2 mRNA upregulation, we find that Myc binds directly to and activates the transcription of the EZH2 promoter. These results link two major pathways in prostate cancer by providing two additional and complementary Myc-regulated mechanisms by which EZH2 upregulation occurs and is enforced during prostatic carcinogenesis. Further, the results implicate EZH2-driven mechanisms by which Myc may stimulate prostate tumor initiation and disease progression.

Mendeley readers

The data shown below were compiled from readership statistics for 70 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 70 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 16 23%
Student > Master 14 20%
Student > Ph. D. Student 13 19%
Student > Bachelor 6 9%
Student > Doctoral Student 6 9%
Other 7 10%
Unknown 8 11%
Readers by discipline Count As %
Agricultural and Biological Sciences 24 34%
Biochemistry, Genetics and Molecular Biology 19 27%
Medicine and Dentistry 14 20%
Veterinary Science and Veterinary Medicine 1 1%
Physics and Astronomy 1 1%
Other 2 3%
Unknown 9 13%