Li Bilan, Lu Wen, Qu Junjie, Zhang Yongli, Wan Xiaoping
Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University, School of Medicine, Shanghai, P.R. China.
J Cancer. 2017 Mar 12;8(6):933-939. doi: 10.7150/jca.17435. eCollection 2017.
Endometrial carcinoma (EC) is one of the most common gynecologic malignancy, but molecular mechanisms of the development and progression of EC remain unclear. Here we showed that the expression of DICER1 was negatively associated with the level of histone methylation, histone acetylation and PRC2 components SUZ12 and EZH2 in EC cells. In addition, knockdown of DICER1 significantly downregulated miR-200b and let-7i, which may then regulate their targets SUZ12 and EZH2. Furthermore, knockdown of DICER1 remarkably suppressed the expression of epithelial cell marker E-cadherin, induced the expression of mesenchymal cell marker Vimentin, and promoted the invasion of EC cells. In conclusion, our data suggest that DICER1 suppresses SUZ12 and EZH2 via affecting their upstream miRNA synthesis, and inhibits epithelial-mesenchymal transition(EMT) and invasion of EC cells via histone modification.
子宫内膜癌（EC）是最常见的妇科恶性肿瘤之一，但其发生发展的分子机制仍不清楚。我们在此表明，DICER1的表达与EC细胞中组蛋白甲基化、组蛋白乙酰化水平以及PRC2组分SUZ12和EZH2呈负相关。此外，敲低DICER1可显著下调miR-200b和let-7i，进而可能调节其靶标SUZ12和EZH2。此外，敲低DICER1显著抑制上皮细胞标志物E-钙黏蛋白的表达，诱导间充质细胞标志物波形蛋白的表达，并促进EC细胞的侵袭。总之，我们的数据表明，DICER1通过影响其上游miRNA合成来抑制SUZ12和EZH2，并通过组蛋白修饰抑制EC细胞的上皮-间质转化（EMT）和侵袭。
