miR-101 was reported to specifically repress expression of EZH2, a conserved catalytic subunit within the polycomb repressor complex 2 (PRC2), which is involved in histone methylation and consequent transcriptional silencing (Varambally et al., 2008; Friedman et al., 2009). Overexpression of miR-101 markedly attenuated cell proliferation and apparently configured the histone code of cancer cells to that associated with more benign cellular phenotypes (Varambally et al., 2008). Other miRNAs commonly silenced in a variety of cancers also target factors in the epigenetic pathway; for example, miR-203 targets Bmi-1, a component of the polycomb repressor complex 1 (PRC1) that working together with PRC2, plays an important role in stabilizing epigenetic gene silencing by binding to methylated chromatin (Wellner et al., 2009; Sato et al., 2011), and miR-152 targets DNA methyltransferase DNMT1 (Tsuruta et al., 2011). All these miRNAs have been postulated as tumor suppressors (TS-miRNAs) and all have in common that they specifically downregulate factors involved in altering the epigenetic landscape of cells. These studies and several others (Rodríguez-Paredes and Esteller, 2011; Tsai and Baylin, 2011) demonstrate that when the epigenetic machinery
