内异症是雌激素依赖的炎性疾病，良性病但具有增殖和侵袭活跃的恶性行为。目前发病机制不清，治疗手段有限。ACC1是调控肿瘤增殖侵袭的重要环节，但对内异症病灶异常增殖和侵袭的作用尚不明确。我们既往研究发现，内异症患者腹腔高表达的炎性因子PGE2通过调控雌激素的合成促进异位病灶的生长，但具体机制不清。我们前期数据显示，ACC1在内异症的异位内膜低表达，PGE2通过MAPK通路抑制ACC1的表达；ACC1被抑制后，PGE2对细胞增殖和侵袭相关因子的表达增强，提示ACC1介导PGE2对内异症的调控。因此，我们拟通过敲低和过表达ACC1，验证ACC1对PGE2及细胞增殖和侵袭的作用；采用免疫共沉淀和染色质免疫沉淀，探讨MAPK下游转录因子与ACC1的结合力；构建异种移植的裸鼠内异症模型，明确ACC1对异位病灶增殖和侵袭的影响。旨在揭示ACC1-PGE2-MAPK-细胞增殖侵袭的具体机制，寻找治疗新靶点。

Endometriosis is an estrogen-dependent inflammatory disease. Although it is a benign disease, it has malignant biological characteristics, such as active proliferation and invasion. At present, the pathogenesis of endometriosis is unclear and therapy methods is still limited. A growing evidence shows strong association between Acetyl-CoA carboxylase 1 (ACC1) and the proliferation and invasion of tumor cells, but the regulation mechanism of ACC1 in endometriosis in not clear yet. Our previously published work demonstrated the abundant PGE2 in the abdominal cavity of patients with endometriosis promotes the growth of ectopic lesions by regulating estrogen metabolism, but the specific mechanism is still unknown. The preliminary experimental data showed that expression of ACC1 were much lower in human ectopic endometrial stromal cells (ESCs) than eutopic endometrial stromal cells (EMs) from the same person. PGE2 stimulated ACC1 expression through MAPK signaling pathway in ESCs. After administration of ACC1 inhibitor TOFA, the promotion effect of PGE2 on proliferation and invasion of endometriotic stromal cells were further up-regulated, suggesting that ACC1 mediates the regulation of PGE2 on endometriosis. To solve these problems, first, by knockdown and overexpression of ACC1, we will verify the possible regulation of PGE2 induced cellular function by ACC1. Secondly, we will further use coimmunoprecipitation assay and chromatin immunoprecipitation to investigate the binding capacity between downstream transcription factors and ACC1. Meanwhile, we will construct xenograft nude mice model of endometriosis and use adenovirus transfection to overexpress ACC1, in order to determine the role of ACC1 on the proliferation and invasion of endometriosis lesions. In conclusion, the aim of the study is to reveal the possible relationship among ACC1, PGE2, MAPK and the proliferation and invasion of endometriosis, and further identifying new molecular targets for the treatment of endometriosis.