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MicroRNA-29 (miR-29); c-Myc (MYC); histone deacetylase 3
(HDAC3); enhancer of zeste homolog 2 (EZH2)

In vitro and mouse studies suggest increasing miR-29 expression by combined inhibition of HDAC3 and EZH2 could help treat MYC-overexpressing cancers. In lymphoma cells, MYC, HDAC3 and EZH2 interacted with the miR-29 promoter region, and MYC upregulation correlated with miR-29 downregulation. In the cells, small interfering RNA targeting HDAC3 and EZH2 increased miR-29 expression and decreased colony formation compared with separate targeting of either HDAC3 or EZH2. In mouse xenograft models of human lymphoma, inhibition or genetic knockdown of HDAC3 and EZH2 decreased tumor size compared with inhibition or knockdown of either target alone.
Next steps include developing HDAC3 and EZH2 inhibitors.
Epizyme Inc. has EZH2 inhibitors including EPZ5687 in preclinical development for cancer.
Constellation Pharmaceuticals Inc. has EZH2 inhibitors in preclinical development for cancer.

SciBX 5(45); doi:10.1038/scibx.2012.1181
Published online Nov. 15, 2012

Unpatented; unavailable for licensing

Zhang, X. et al. Cancer Cell; published online Oct. 16, 2012;
Contact: Jianguo Tao, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla.