EZH2 directly interacts with histone deacetylases (Simon and Lange, 2008; Zhang et al., 2015) and DNA methylases (Viré et al., 2006; Liu et al., 2018; Tiffen et al., 2020), and its non-canonical activity comprises methylation and thus activation of non-histone proteins, such as signal transducer and activator of transcription 3 (STAT3) in glioblastoma (Kim et al., 2013) or androgen receptor (AR) in castration-resistant prostate cancer (Xu et al., 2012; Kim et al., 2018), and this activity is PRC2-independent. This evidence concerns the gene STAT3 and glioblastoma.