Alzrigat Mohammad, Jernberg-Wiklund Helena
Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, SE-751 85, Sweden.
RNA Dis. 2017;4(2). doi: 10.14800/rd.1529. Epub 2017 Apr 3.
We have previously presented the histone methyltransferase enhancer of zeste homolog 2 (EZH2) of the polycomb repressive complex 2 (PRC2) as a potential therapeutic target in Multiple Myeloma (MM). In a recent article in Oncotarget by Alzrigat. . 2017, we have reported on the novel finding that EZH2 inhibition using the highly selective inhibitor of EZH2 enzymatic activity, UNC1999, reactivated the expression of microRNA genes previously reported to be underexpressed in MM. Among these, we have identified miR-125a-3p and miR-320c as potential tumor suppressor microRNAs as they were predicted to target MM-associated oncogenes; IRF-4, XBP-1 and BLIMP-1. We also found EZH2 inhibition to reactivate the expression of miR-494, a previously reported regulator of the c-MYC oncogene. In addition, we could report that EZH2 inhibition downregulated the expression of a few well described oncogenic microRNAs in MM. The data from our recent article are here highlighted as it shed a new light onto the oncogenic function of the PRC2 in MM. These data further strengthen the notion that the PRC2 complex may be of potential therapeutic interest.
我们之前已提出，多梳抑制复合物2（PRC2）中的组蛋白甲基转移酶zeste同源物2（EZH2）是多发性骨髓瘤（MM）的一个潜在治疗靶点。在Alzrigat等人于2017年发表在《Oncotarget》上的一篇近期文章中，我们报道了一项新发现，即使用EZH2酶活性的高度选择性抑制剂UNC1999抑制EZH2可重新激活先前报道在MM中表达不足的微小RNA基因的表达。其中，我们已鉴定出miR-125a-3p和miR-320c为潜在的肿瘤抑制微小RNA，因为它们预计靶向MM相关的致癌基因；IRF-4、XBP-1和BLIMP-1。我们还发现抑制EZH2可重新激活miR-494的表达，miR-494是先前报道的c-MYC致癌基因的调节因子。此外，我们可以报告，抑制EZH2可下调MM中一些已充分描述的致癌微小RNA的表达。我们近期文章中的数据在此突出展示，因为它为PRC2在MM中的致癌功能提供了新的线索。这些数据进一步强化了PRC2复合物可能具有潜在治疗价值的观点。
