In agreement with the findings that both PcD and PcI functions of EZH2 require the methyltransferase activity [16], we demonstrated that treatment of the EZH2 inhibitor GSK126 not only causes de-repression of EZH2-repressed genes such as BRACHYURY, HOXA9, DAB2IP and FOXJ1, but also downregulates the expression of EZH2-activated genes such as TMEM48, CSK2 and KIAA0101. Thus, the anti-tumor effect of EZH2 inhibitors is likely attributed to their inhibition of both PcD and PcI functions of EZH2. Here, EZH2 is linked to neoplasm.