Cancer Research-UK Laboratories, Division of Cancer, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK.
J Endocrinol. 2012 Jan;212(1):13-25. doi: 10.1530/JOE-10-0480. Epub 2011 Mar 7.
The rise and fall in ovarian oestrogen and progesterone production orchestrates a series of events that are indispensable for reproduction, including ovulation, implantation, decidualisation and menstruation. In the uterus, these events involve extensive tissue remodelling, characterised by waves of endometrial cell proliferation, differentiation, recruitment of inflammatory cells, apoptosis, tissue breakdown, menstruation and regeneration. The ability of ovarian hormones to trigger such diverse physiological responses is foremost dependent upon interaction of activated steroid receptors with specific transcription factors, such as Forkhead box class O (FOXO) proteins, involved in cell fate decisions. Furthermore, micro-RNAs (miRNAs), small non-coding RNAs that function as posttranscriptional regulators of gene expression, have emerged as a major regulator system of steroid hormone responses in the female reproductive tract. Consequently, increasing evidence shows that deregulated uterine miRNA expression underpins a spectrum of common reproductive disorders, ranging from implantation failure to endometriosis. Furthermore, by targeting FOXO transcription factors and other key regulators of tissue homeostasis, oncogenic endometrial miRNAs promote tumourigenesis and cancer progression.
卵巢雌激素和孕激素的产生的起伏变化，精心安排了一系列对生殖至关重要的事件，包括排卵、着床、蜕膜化和月经。在子宫中，这些事件涉及广泛的组织重塑，其特征是子宫内膜细胞增殖、分化、募集炎症细胞、细胞凋亡、组织破坏、月经和再生的波浪式变化。卵巢激素引发如此多样化的生理反应的能力主要取决于激活的甾体激素受体与特定转录因子（如参与细胞命运决定的叉头框 O 类（FOXO）蛋白）的相互作用。此外，微小 RNA（miRNA），作为基因表达转录后调控因子的小非编码 RNA，已成为女性生殖道中甾体激素反应的主要调控系统。因此，越来越多的证据表明，子宫 miRNA 表达失调是一系列常见生殖障碍的基础，从着床失败到子宫内膜异位症。此外，通过靶向 FOXO 转录因子和其他组织稳态的关键调节剂，致癌性子宫内膜 miRNA 促进肿瘤发生和癌症进展。
