MicroRNA-372 inhibits endometrial carcinoma development by targeting the expression of the Ras homolog gene family member C (RhoC).
MicroRNA-372 inhibits endometrial carcinoma development by targeting the expression of the Ras homolog gene family member C (RhoC).
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MicroRNA-372 通过靶向 Ras 同源基因家族成员 C (RhoC) 的表达抑制子宫内膜癌的发展
DOI：
10.18632/oncotarget.6544
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发表时间：
2016-02-09
期刊：
影响因子：
--
通讯作者：
Zhao Y
中科院分区：
文献类型：
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作者：
Liu BL;Sun KX;Zong ZH;Chen S;Zhao Y
在此，我们探讨microRNA-372（miR-372）在子宫内膜腺癌（EC）肿瘤发生和发展中的作用并分析其潜在机制。我们发现 miR-372 的表达在 EC 中比正常子宫内膜标本低得多。细胞功能实验表明，miR-372过表达可抑制子宫内膜癌细胞的增殖、迁移和侵袭，导致G1期阻滞并促进子宫内膜癌细胞凋亡。裸鼠异种移植试验表明，miR-372 过表达可抑制肿瘤生长。 RT-PCR和Western blot检测检测了miR-372已知靶标在其他恶性肿瘤中的表达，发现Cyclin A1和Cyclin依赖性激酶2（CDK2）被miR-372下调。生物信息学预测和双荧光素酶报告基因检测发现 RhoC 是 miR-372 的可能靶标。 RT-PCR 和 Western blot 检测表明，miR-372 转染降低了 RhoC、基质金属蛋白酶 2 (MMP2) 和 MMP9 的表达，同时增加了裂解聚 (ADP 核糖) 聚合酶 (PARP) 和 bcl-2 相关 X 蛋白 (Bax) 的表达。 RhoC转染siRNA的细胞功能实验与转染miR-372的细胞功能实验显示出相同的趋势。总而言之，我们的结果首次证明 miR-372 抑制肿瘤发生和 EC 的发展； RhoC 是一个新的、潜在的重要治疗靶点。
Here we explore the role of microRNA-372 (miR-372) in tumorigenesis and development of endometrial adenocarcinoma (EC) and analyze the underlying mechanism. We found that miR-372 expression is much lower in EC than normal endometrial specimens. Cell function experiments demonstrated that miR-372 overexpression suppressed cell proliferation, migration, and invasion, and led to a G1 phase arrest and promoted the apoptosis of endometrial carcinoma cells in vitro. The nude mouse xenograft assay demonstrated that miR-372 overexpression suppressed tumor growth. RT-PCR and Western blot assays detected the expression of known targets of miR-372 in other malignant tumors and found Cyclin A1 and Cyclin-dependent Kinase 2 (CDK2) was downregulated by miR-372. Bioinformatic predictions and dual-luciferase reporter assays found that RhoC was a possible target of miR-372. RT-PCR and Western blot assays demonstrated that miR-372 transfection reduced the expression of RhoC, matrix metalloproteinase 2 (MMP2) and MMP9, while it increased the expression of cleaved poly (ADP ribose) polymerase (PARP) and bcl-2-associated X protein (Bax). The cell function experiments that transfected siRNA with RhoC showed the same trend as those which were transfected with miR-372. Taken together, our results demonstrated for the first time that miR-372 suppresses tumorigenesis and the development of EC; RhoC is a new and potentially important therapeutic target.