Polycomblike2 (PCL2) is a well-known component of polycomb repressive complex 2 (PRC2) and plays important roles in H3K27 methylation and homeotic gene silencing. However, the involvement of PCL2 in breast cancer development remains unclear. Here, we established PCL2 as a tumor suppressor gene in breast cancer. Expression level of PCL2 was significantly downregulated in breast cancer tissue samples observed at different TNM stages. Ectopic expression of PCL2 could significantly inhibit cell proliferation and promoted apoptosis. PCL2 also remarkably elevated levels of p53 and its targets by increasing p53 stability. Mechanistically, PCL2 protected p53 proteins from MDM2-mediated ubiquitination and degradation by sequestering MDM2 into the nucleolus. Overexpression of PCL2 also suppressed migration and invasion by inhibiting epithelial-mesenchymal transition. PCL2 expression was correlated with E-cadherin expression and was inversely correlated with vimentin expression. Furthermore, PCL2 knockdown could attenuate anti-tumor effect of MLN4924. Taken together, our findings indicated that PCL2 played a tumor suppressor role in development and progression of breast cancer and may be a prognostic and predictive marker for breast cancer.

Polycomblike2 (PCL2) 是多梳抑制复合物 2 (PRC2) 的一个众所周知的成分，在 H3K27 甲基化和同源异型基因沉默中起着重要作用。然而，PCL2 在乳腺癌发展中的作用仍不清楚。在这里，我们将 PCL2 确定为乳腺癌的抑癌基因。在不同 TNM 阶段观察到的乳腺癌组织样本中 PCL2 的表达水平显着下调。PCL2的异位表达可显着抑制细胞增殖并促进细胞凋亡。PCL2 还通过增加 p53 稳定性显着提高 p53 及其靶标的水平。从机制上讲，PCL2 通过将 MDM2 隔离到核仁中来保护 p53 蛋白免受 MDM2 介导的泛素化和降解。PCL2 的过表达还通过抑制上皮-间质转化来抑制迁移和侵袭。PCL2 表达与 E-钙粘蛋白表达相关，与波形蛋白表达呈负相关。此外，PCL2 敲低可减弱 MLN4924 的抗肿瘤作用。综上所述，我们的研究结果表明 PCL2 在乳腺癌的发生和发展过程中发挥了抑癌作用，可能是乳腺癌的预后和预测标志物。