Luminal乳腺癌是女性最常见的恶性肿瘤，其特异的超级增强子lncRNA（SE-lncRNA）可能在该肿瘤进展中起到重要作用，但功能机制尚不清楚。我们前期发现SE-lncRNA NCALD在Luminal乳腺癌中特异高表达；雌激素/雌激素受体α（E2/ERα）可结合其启动子区刺激其表达并促进乳腺癌进展；干扰SE-lncRNA NCALD可抑制GRHL2基因表达；数据库预测SE-lncRNA NCALD可能影响GRHL2基因超级增强子区，且受影响区具有ERα结合点。故我们推测：E2/ERα诱导SE-lncRNA NCALD表达，三者形成复合体结合GRHL2的超级增强子区促进GRHL2上调，影响肿瘤进展。本项目拟从分子、细胞、组织水平全面阐明SE-lncRNA NCALD在Luminal乳腺癌中的功能及上下游调控机制，为研发Luminal乳腺癌新型生物标志物及靶向药物提供新方向。

Luminal breast cancer is one of the most common malignancies in clinical practice and specific super-enhancer-associated long non-coding RNA (SE-lncRNA) of luminal breast cancer may play the key role in tumor progression. However, roles and mechanisms of SE-lncRNA in luminal breast cancer are unknown. In previous study, we identified a novel SE-lncRNA whose expression is high in breast cancer and especially higher in luminal breast cancer, dubbed SE-lncRNA NCALD. Knocking down SE-lncRNA NCALD can inhibit tumor proliferation and metastasis. Further analysis of luminal breast cancer cells showed that estrogen (E2) and estrogen receptor (ERα) may regulate SE-lncRNA NCALD by activation of its promoter and super-enhancer. Meanwhile, SE-lncRNA NCALD shRNA could decrease GRHL2 expression. In addition, the database suggested that SE-lncRNA NCALD may affect super-enhancers of GRHL2 and the super-enhancers of GRHL2 have ERα binding site. Therefore, we propose E2 and ERαmay regulate SE-lncRNA NCALD expression, SE-lncRNA NCALD may form complex with E2 and ERα to regulate GRHL2 expression by binding to the super-enhancers of GRHL2, which ultimately promotes the progression of luminal breast cancer. This project aims to clarify the mechanisms and clinical significances of SE-lncRNA NCALD in the progression of luminal breast cancer from molecular level, cell level and tissue level. Our study can provide new ideas for the development of luminal breast cancer treatment drugs and exploration of new biomarkers.