XIST基因在小鼠子宫衰老过程中的作用和机制研究

The molecular mechanism underlying uterine aging remains undefined. Previously, we discovered that XIST RNA was significantly decreased aged uterus, along with DNA hypermethylation near the promoter region. Using in vitro models, we found that XIST was involved in decidualization process and was likely a driver gene for uterine aging. XIST is a well-known long non-coding RNA with a role in X chromosome inactivation. Recent studies have suggested that XIST may also play an important role during tumorigenesis. Here, we link XIST with aging for the first time. In this study, using XIST conditional knockout mice, we are going to explore the function of XIST in mouse uterus during aging and decidualization. Moreover, the RBP (RNA binding protein) and ceRNA (competing endogenous RNA) hypotheses will be tested to explain the observed function of XIST in uterus. Finally, we will investigate the role of DNA methylation on uterine expression of XIST. Our study may help to understand the molecular mechanism underlying uterine aging and provide implications for the development of anti-aging therapy.

子宫衰老的分子机制目前仍不清楚。我们通过前期研究发现，XIST基因在衰老小鼠子宫中表达下调，同时近启动子区DNA甲基化上调。通过体外模型，我们发现XIST参与蜕膜化过程并且可能是子宫衰老的驱动基因。作为一个最早被研究的长链非编码RNA，XIST的作用长期被限制为X染色体失活。最近几年的研究证明XIST在肿瘤发生发展中发挥重要的作用。在此，我们首次将XIST与子宫衰老联系起来。本研究拟以子宫特异性XIST敲除小鼠为基础，通过体内模型和体外模型，对XIST基因在子宫衰老和蜕膜化过程中的作用进行细致研究。进一步的，我们将围绕RBP假说和ceRNA假说进行XIST作用机制的探索。最后，我们将研究DNA甲基化对XIST表达的调节。本项目的实施将有助于进一步了解子宫衰老的分子机理，为开发延缓雌性生殖衰老的措施提供理论依据。

作为一个最早被研究的长链非编码RNA，XIST的作用长期被限制为X染色体失活。最近几年的研究表明XIST在肿瘤发生发展中发挥重要的作用。在此，我们首次将XIST与子宫衰老联系起来。我们研究发现，XIST基因在衰老小鼠子宫中表达下调，同时近启动子区域DNA甲基化水平上调。通过体内模型和体外模型，我们证明XIST基因在子宫衰老和蜕膜化过程中发挥重要的作用。我们围绕RBP假说和ceRNA假说对XIST的作用机制进行了解读。最后，我们发现子宫中XIST的表达受DNA甲基化调节。本项目的研究成果有助于进一步了解子宫衰老的分子机理，为开发延缓雌性生殖衰老的措施提供理论依据。