Department of Obstetrics and Gynecology, University of Florida, Gainesville, FL 32610, USA.
Reprod Sci. 2012 Aug;19(8):786-96. doi: 10.1177/1933719112438448. Epub 2012 May 8.
A number of microRNAs (miRNAs), including miR-200 family, are aberrantly expressed in endometriosis and endometrial cancer. Here we assessed the expression and functional aspects of miR-200c in endometrial tissues (N = 52) from normal endometrial biopsies (N = 15), endometrial tissues including those exposed to hormonal therapies (N = 20), and grade I-III endometrial cancer (N = 17). miR-200c expression was elevated in normal endometrial biopsies from mid- and late-luteal phase, and in endometrial tumors as compared to endometrial tissues from peri- and postmenopausal period (P < .05) and its pattern of temporal expression displayed an inverse relationship with the expression of ZEBs. The expression of E-cadherin (CDH1) varied, but expressed at low levels, specifically in endometrial tissues and endometrial tumors. The endometrial expression of ZEBs and CDH1 in patients who were exposed to Depo-Provera and gonadotropin-releasing hormone agonist GnRHa displayed a trend toward lower expression as compared to proliferative phase; however, treatment of Ishikawa cells with 17β-estradiol, progesterone, and medroxy progesterone acetate had modest effects on the expression of miR-200c and ZEBs without affecting CDH1 expression. Gain of function of miR-200c in Ishikawa cells repressed ZEBs, as well as VEGFA, FLT1, IKKβ, and KLF9 expression at transcriptional and translational levels through direct interaction with their respective 3'untranslated regions and increased the rate of their proliferation. These results indicated that endometrial miR-200c expression undergoes dynamic changes during transition from normal into cancerous states; possibly influenced by hormonal milieu and by targeting the expression of specific genes with key regulatory functions in cellular transformation, inflammation, and angiogenesis may influence these events during normal and disease progression.
许多 microRNAs（miRNAs），包括 miR-200 家族，在子宫内膜异位症和子宫内膜癌中表达异常。在这里，我们评估了 miR-200c 在子宫内膜组织中的表达和功能方面（N = 52），包括来自正常子宫内膜活检（N = 15）、接受激素治疗的子宫内膜组织（N = 20）和 I-III 级子宫内膜癌（N = 17）。与围绝经期和绝经后子宫内膜组织相比，miR-200c 在中晚期黄体期的正常子宫内膜活检和子宫内膜肿瘤中的表达升高（P <.05），其时间表达模式与 ZEBs 的表达呈负相关。E-钙粘蛋白（CDH1）的表达不同，但表达水平较低，特别是在子宫内膜组织和子宫内膜肿瘤中。与增殖期相比，接受 Depotrovera 和促性腺激素释放激素激动剂 GnRHa 治疗的患者的子宫内膜组织中 ZEBs 和 CDH1 的表达呈下降趋势；然而，17β-雌二醇、孕酮和醋酸甲羟孕酮对 Ishikawa 细胞中 miR-200c 和 ZEBs 的表达只有适度影响，而不影响 CDH1 的表达。miR-200c 在 Ishikawa 细胞中的功能获得通过与各自的 3'非翻译区直接相互作用，在转录和翻译水平上抑制 ZEBs 以及 VEGFA、FLT1、IKKβ 和 KLF9 的表达，并增加其增殖率。这些结果表明，子宫内膜 miR-200c 的表达在从正常状态向癌状态转变过程中发生动态变化；可能受激素环境影响，并通过靶向具有细胞转化、炎症和血管生成关键调节功能的特定基因的表达，影响正常和疾病进展过程中的这些事件。
