MicroRNA-298 inhibits malignant phenotypes of epithelial ovarian cancer by regulating the expression of EZH2.
MicroRNA-298 inhibits malignant phenotypes of epithelial ovarian cancer by regulating the expression of EZH2.
复制标题
DOI：
10.3892/ol.2016.5204
复制
发表时间：
2016-11
期刊：
影响因子：
2.9
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Zhou F;Chen J;Wang H
据报道，MicroRNA (miRNA或miR)-298在复发性上皮性卵巢癌（EOC）中下调并改变zeste 2多梳蛋白增强子（EZH2）的表达。迄今为止，没有证据表明miR-298-EZH2轴在EOC中具有功能性。本研究旨在探讨miR-298和/或EZH2表达与EOC患者临床病理特征的关系，并基于EOC细胞系揭示其在细胞运动中的作用。采用逆转录-定量聚合酶链反应检测miR-298和EZH2信使RNA在人EOC组织和细胞系中的表达水平。通过伤口愈合和transwell实验分别确定miR-298-EZH2轴对细胞迁移和侵袭的功能。与正常组织相比，人EOC组织中miR-298的表达显著下调，EZH2的表达显著上调（P均=0.001）。此外，miR-298下调和EZH2上调与EOC患者的高临床分期（P=0.01）和病理分级（P=0.02）显著相关。此外，miR-298的异位表达可以有效抑制细胞的迁移和侵袭。值得注意的是，过表达EZH2可以恢复被miR-298抑制的细胞迁移和侵袭能力。我们的数据提供了令人信服的证据，表明miR-298-EZH2轴的失调可能在EOC患者的肿瘤进展中很重要。本研究还证实了miR-298通过调节EZH2的表达来调节EOC细胞运动的肿瘤抑制作用，这意味着它有可能成为治疗人类EOC的一种新的基于mirna的治疗靶点。
MicroRNA (miRNA or miR)-298 has been reported to be downregulated and to modify the expression of the polycomb protein enhancer of zeste 2 (EZH2) in recurrent epithelial ovarian cancer (EOC). To date, no functional evidence of a miR-298-EZH2 axis in EOC has been documented. The present study aimed to investigate the associations of miR-298 and/or EZH2 expression with clinicopathological features of EOC patients, and revealed their roles in cell motility based on EOC cell lines. Reverse transcription-quantitative polymerase chain reaction was performed to detect the expression levels of miR-298 and EZH2 messenger RNA in human EOC tissues and cell lines. Wound healing and transwell assays were performed to determine the function of the miR-298-EZH2 axis on cell migration and invasion, respectively. Compared with normal tissues, miR-298 expression was significantly downregulated, while EZH2 expression was significantly upregulated, in human EOC tissues (both P=0.001). In addition, miR-298 downregulation and EZH2 upregulation were significantly associated with high clinical stage (both P=0.01) and pathological grade (both P=0.02) of EOC patients. Furthermore, the ectopic expression of miR-298 could efficiently inhibit cell migration and invasion. Notably, the overexpression of EZH2 could restore the cell migration and invasion abilities suppressed by miR-298. Our data offer convincing evidence that the dysregulation of the miR-298-EZH2 axis may be important in tumor progression of EOC patients. The present study also confirmed a tumor-suppressive role of miR-298 in modulating EOC cell motility by regulating the expression of EZH2, implying its potential as a novel miRNA-based therapeutic target for the treatment of human EOC.
登录
查看更多内容
DOI：
10.1038/nrclinonc.2013.5
发表时间：
2013-04
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
通讯作者：
--
多梳蛋白证明上皮性卵巢癌复发中的肿瘤异质性
影响因子：
4
作者：
Gui T;Bai H;Zeng J;Zhong Z;Cao D;Cui Q;Chen J;Yang J;Shen K
通讯作者：
Shen K
影响因子：
4
作者：
Zaman MS;Maher DM;Khan S;Jaggi M;Chauhan SC
通讯作者：
Chauhan SC
影响因子：
6
作者：
Bao, Lili;Hazari, Sidhartha;Dash, Srikanta
通讯作者：
Dash, Srikanta
影响因子：
6.4
作者：
Yeh, Yu-Ming;Chuang, Chi-Mu;Wang, Lu-Hai
通讯作者：
Wang, Lu-Hai