Lu Zheng, Nian Zhou, Jingjing Zhang, Tao Luo, Quan Li
Department of Gynaecology, The First Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
Oncotarget. 2017 Dec 13;8(69):114281-114291. doi: 10.18632/oncotarget.23218. eCollection 2017 Dec 26.
Our previous study explored the roles of microRNA-424 (miR-424) in the development of endometrial carcinoma (EC) and analyzed the miR-424/E2F7 axis in EC cell growth. In this study, we investigated the status of miR-424 in human endometrial cancer tissues, which were collected from a cohort of Zunyi patients. We found that the expression level of miR-424 was associated with clinical tumor stage, cell differentiation, lymph node metastasis and cell migration ability. Cell function experiments demonstrated that miR-424 overexpression suppressed the invasion and migration abilities of endometrial carcinoma cells . Bioinformatic predictions and dual-luciferase reporter assays suggested E2F6 as a possible target of miR-424. RT-PCR and western blot assays demonstrated that miR-424 transfection reduced the expression level of E2F6, while inhibiting miR-424 with ASO-miR-424 (antisense oligonucleotides of miR-424) increased the expression level of E2F6. Cell function experiments indicated that E2F6 transfection rescued the EC cell phenotype induced by miR-424. In addition, we also found that E2F6 negatively regulated miR-424 expression in EC cells. In summary, our results demonstrated that the miR-424/E2F6 feedback loop modulates cell invasion, migration and EMT in EC and that the miR-424/E2Fs regulation network may serve as a new and potentially important therapeutic target in EC.
我们之前的研究探讨了微小RNA - 424（miR - 424）在子宫内膜癌（EC）发生发展中的作用，并分析了miR - 424/E2F7轴在EC细胞生长中的作用。在本研究中，我们调查了从一组遵义患者收集的人子宫内膜癌组织中miR - 424的状态。我们发现miR - 424的表达水平与临床肿瘤分期、细胞分化、淋巴结转移及细胞迁移能力相关。细胞功能实验表明，miR - 424过表达抑制了子宫内膜癌细胞的侵袭和迁移能力。生物信息学预测和双荧光素酶报告基因检测表明E2F6可能是miR - 424的一个靶标。RT - PCR和蛋白质印迹分析表明，miR - 424转染降低了E2F6的表达水平，而用ASO - miR - 424（miR - 424的反义寡核苷酸）抑制miR - 424则增加了E2F6的表达水平。细胞功能实验表明，E2F6转染挽救了由miR - 424诱导的EC细胞表型。此外，我们还发现E2F6在EC细胞中负调控miR - 424的表达。总之，我们的结果表明，miR - 424/E2F6反馈环调节EC中的细胞侵袭、迁移和上皮 - 间质转化（EMT），并且miR - 424/E2Fs调控网络可能作为EC中一个新的且潜在重要的治疗靶点。
