DICER1 regulates endometrial carcinoma invasion via histone acetylation and methylation.
DICER1 regulates endometrial carcinoma invasion via histone acetylation and methylation.
复制标题
DICER1 通过组蛋白乙酰化和甲基化调节子宫内膜癌侵袭。
DOI：
10.7150/jca.17435
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发表时间：
2017
影响因子：
3.9
通讯作者：
Wan X
中科院分区：
文献类型：
--
作者：
Li B;Lu W;Qu J;Zhang Y;Wan X
子宫内膜癌（Endometrial carcinoma，EC）是妇科最常见的恶性肿瘤之一，但其发生发展的分子机制尚不清楚。我们发现DICER 1的表达与EC细胞中组蛋白甲基化、组蛋白乙酰化和PRC 2组分SUZ 12和EZH 2的水平呈负相关。此外，DICER 1的敲低显著下调了miR-200 b和let-7i，这可能随后调节其靶点SUZ 12和EZH 2。此外，DICER 1基因的敲低可显著抑制上皮细胞标志物E-cadherin的表达，诱导间充质细胞标志物Vimentin的表达，促进EC细胞的侵袭。总之，我们的数据表明，DICER 1通过影响SUZ 12和EZH 2上游miRNA的合成来抑制SUZ 12和EZH 2，并通过组蛋白修饰来抑制上皮-间质转化（EMT）和EC细胞的侵袭。
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.