Chen Zhen, Zhu Yingjun, Fan Xiaodong, Liu Yabo, Feng Qingqing
Department of General Gynaecology, Tianjin Central Hospital of Gynecology and Obstetrics Tianjin 300100, China.
Am J Transl Res. 2019 Feb 15;11(2):755-764. eCollection 2019.
Endometrial carcinoma (EC) is one of the most common malignancies of female reproductive tract in developed countries. MicroRNA is frequently dysregulated in human cancers and acts a key regulator role in tumor cell growth and metastasis. The aims of this study were to investigate the roles of microRNA-184 (miR-184) in EC cells and to identify its potential molecular mechanism. Here, the data revealed that miR-184 was significantly downregulated in human EC tissue compared with normal endometrial tissue, and the level of miR-184 expression was associated with lymph node metastasis and prognosis in patients with EC. In vitro assays, overexpression of miR-184 could suppress the proliferation and invasion of HEC-1B and RL95-2 cells. Moreover, bioinformatics analysis showed that cell division cycle 25A (CDC25A) was a putative target gene of miR-184. Dual luciferase reporter assay confirmed that miR-184 significantly downregulated CDC25A expression via directly interaction with the putative binding site in the 3'-untranslated region (3'-UTR) of CDC25A mRNA. Interestingly, knockdown of CDC25A resulted in inhibition of HEC-1B and RL95-2 cells growth and invasion. Mechanistic investigation revealed that downregulation of the Notch receptors (NOTCH1, NOTCH2, NOTCH3 and NOTCH4) and target gene HES1 by miR-184 could be reversed by CDC25A overexpression. In summary, our data demonstrate that CDC25A is a target gene of miR-184 in EC cells, and decreased expression of miR-184 suppresses the growth and invasion of EC cells via CDC25A-dependent Notch signaling pathway, suggesting that miR-184 may be a promising target for a new therapeutic strategy against EC.
子宫内膜癌（EC）是发达国家女性生殖道最常见的恶性肿瘤之一。微小RNA在人类癌症中经常失调，并在肿瘤细胞生长和转移中起关键调节作用。本研究的目的是探讨微小RNA-184（miR-184）在EC细胞中的作用，并确定其潜在的分子机制。在此，数据显示与正常子宫内膜组织相比，miR-184在人类EC组织中显著下调，且miR-184的表达水平与EC患者的淋巴结转移及预后相关。体外实验表明，miR-184过表达可抑制HEC-1B和RL95-2细胞的增殖和侵袭。此外，生物信息学分析表明细胞分裂周期25A（CDC25A）是miR-184的一个潜在靶基因。双荧光素酶报告基因实验证实，miR-184通过与CDC25A mRNA的3'-非翻译区（3'-UTR）中的假定结合位点直接相互作用，显著下调CDC25A的表达。有趣的是，敲低CDC25A可导致HEC-1B和RL95-2细胞生长和侵袭受到抑制。机制研究表明，miR-184对Notch受体（NOTCH1、NOTCH2、NOTCH3和NOTCH4）和靶基因HES1的下调作用可被CDC25A过表达逆转。总之，我们的数据表明CDC25A是EC细胞中miR-184的靶基因，miR-184表达降低通过CDC25A依赖的Notch信号通路抑制EC细胞的生长和侵袭，提示miR-184可能是针对EC的新治疗策略的一个有前景的靶点。
