LINC00673调控HIF-1α促进Warburg effect在子宫内膜蜕膜化中的作用和机制研究

子宫内膜蜕膜化异常是引起胚胎反复种植失败（RIF）的重要原因，但蜕膜化调控机制尚不完全清楚。我们前期预实验发现，RIF患者分泌中期内膜组织中LINC00673、Warburg effect关键调控基因HIF-1α和蜕膜化标记基因表达异常升高。由此，我们推测LINC00673调控HIF-1α促进内膜过度蜕膜化而引起种植失败。本课题首先分析临床样本中LINC00673及HIF-1α表达，明确LINC00673与HIF-1α相关性；随后采用RNA Pull-down、RIP、ChIP等实验，在细胞模型中探究LINC00673调控HIF-1α的分子机制；最后在动物模型中改变LINC00673表达后分析对小鼠内膜蜕膜化和胚胎种植的影响，揭示调节LINC00673的表达可改善胚胎种植。本研究阐明LINC00673在蜕膜化过程中的作用，为RIF患者病因提供新的理论依据及诊疗策略，有重要的潜在应用价值。

Endometrial decidualization is crucial for embryos implantation, but the molecular mechanism of endometrial decidualization process are not fully understand. Our preliminary results suggested that the expression of LINC00673, HIF-1α and the biomarker of decidualization gene are significantly higher. Hence, we hypothesized that LINC00673 might promote abnormality of endometrial decidualization by up-regulating HIF-1α pathway, resulted in the embryo implantation failure. To verify the hypothesis, our study attempts to perform the following researches: firstly, the expression LINC00673 and HIF-1α will be analyzed in clinical samples by mRNA microarray, quantitative PCR and Western blot between control and RIF groups, to confirm the relationship between LINC00673 and HIF-1α; secondly, the regulatory molecular mechanism of LINC00673 regulating HIF-1α explore by RNA Pull-down, RNA immunoprecipitation, Chromatin immunoprecipitation assays; lastly, the endometrial decidualization and clinical outcomes will be assessed using the RIF mouse model after knock-down the LINC00673 and its target gene HIF-1α expression. This study will help us to improve the understanding of etiology of endometrial decidualization on embryo implantation, and may be provide a novel candidate diagnostic hallmark and a potential therapeutic target for early treatment.