虽然以雌激素及其受体为基础的子宫内膜癌（内膜癌）致病理论能够解释雌激素促进内膜癌细胞增殖的原因，但不能解释增殖的细胞发生恶性转化的机制。NORAD是能够维持肿瘤细胞染色体稳定性的长链非编码RNA。由于雌激素是内膜癌确认的致癌因子，且染色体不稳定性是肿瘤恶性转化的重要特征，推测雌激素可以不通过其受体途径、而是通过调节NORAD的表达导致染色体不稳定。预实验结果显示：雌激素能够下调内膜癌细胞长链非编码RNA-NORAD；NORAD与FUBP1复合体被阻滞于内膜癌细胞的胞质中；干扰NORAD表达能诱发内膜癌细胞的染色体不稳定。本项研究将证明雌激素调节NORAD的表观遗传调控机制；观察NORAD的结合蛋白FUBP1对染色体不稳定性的影响；探索雌激素是否独立于其相应受体实现对NORAD的调控。以上假想的证实将会丰富雌激素的内膜癌致癌理论，为lncRNA相关的分子靶向治疗提供有价值的实验基础。

The classical theory of endometrial carcinogenesis based on estrogen and estrogen receptor(ER) interaction can explain how they promote cell proliferation. However, the theory can’t explain mechanism of cell malignant transformation. In fact, chromosomal instability is accepted as the major driver of cell malignant transformation. Most recently, a study found a long non-coding RNA NORAD that was involved in maintaining genomic stability. As estrogen has been identified as an oncogenic factor in endometrial carcinoma, we speculate that estrogen leads to chromosomal instability via regulation the expression of NORAD independent of its classical receptor. Our pre-experiment results show that: (1) Estrogen downregulates NORAD expression through DNA methylation. (2) NORAD directly binds with FUBP1 and sequesters it in the cytoplasm. (3) Knockdown of NORAD leads to chromosomal instability. We aim to elucidate the following points by performing corresponding experiments: (1) Mechanism of how estrogen epigenetically regulates NORAD expression. (2) The effect of FUBP1 on chromosomal instability. (3) Whether estrogen regulates NORAD expression independent of estrogen receptor. Our studies will further supplement the role of estrogen in endometrial carcinogenesis. Notably, lncRNA NORAD may be a promising therapeutic target.