雌激素通过调控EZH2/miR-152/E2F7轴促进ER+乳腺癌进展的机制研究

雌激素信号是促发雌激素受体阳性（ER+）乳腺癌的主要诱因，但其介导乳腺癌进展新的分子机制尚未完全阐明。我们的前期研究表明在ER+乳腺癌中，雌激素能够诱导组蛋白甲基转移酶EZH2的表达促进细胞增殖，本课题组已证实miR-152促进乳腺癌新的血管生成。据此我们认为雌激素通过上调EZH2表达，后者通过表观遗传学修饰抑制miR-152的表达，削弱其对靶基因E2F7的抑制作用，而E2F7作为转录因子又能促进EZH2的表达，进而形成一个反馈通路，促进ER+乳腺癌的进展。本项目从公共数据库挖掘、细胞生物学实验、动物学实验和临床样本四个层面，深入探讨雌激素通过调控EZH2/miR-152/E2F7反馈通路促进ER+乳腺癌进展的机制，为ER+乳腺癌的早期诊断和治疗提供新的研究思路和潜在的分子靶点。

Estrogen signaling is the main inducement of estrogen receptor-positive（ER+） breast cancer, but the new molecular mechanism of estrogen-mediated breast cancer progression has not yet been fully elucidated. Our previous studies have shown that in ER+ breast cancer, estrogen induces the expression of histone methyltransferase EZH2 to promote cell proliferation. Our group has confirmed that miR-152 promotes new angiogenesis in breast cancer. Based on this, we believe that estrogen up-regulates the expression of EZH2, which inhibits the expression of miR-152 through epigenetic modification, weakening its inhibitory effect on the target gene E2F7, and E2F7 as a transcription factor can promote the expression of EZH2, thereby forming A feedback pathway that promotes the progression of ER+ breast cancer. This project deeply explores the molecular mechanism of estrogen-mediated EZH2/miR-152/E2F7 feedback pathway on breast cancer progression from public database mining, cell biology experiments, zoology experiments and clinical samples. For the early diagnosis and treatment of breast cancer provide new research ideas and potential molecular targets.