环状RNA调控miRNA和基因的表达，与肿瘤的发生发展密切相关。申请者前期证实miR-200b具有抗肿瘤作用，可抑制三阴乳腺癌的生长与转移。本项目通过环状RNA芯片和预实验发现，crEPSTI1在三阴乳腺癌中表达升高，过表达crEPSTI1可下调miR-200b和miR-4753，促进三阴乳腺癌细胞增殖与侵袭。生物信息学预测SOX2是miR-200b和miR-4753的共同靶基因；进一步实验发现crEPSTI1可与SRC结合，文献证实SRC可促进SOX2表达。由此我们提出科学假说：crEPSTI1可通过吸附miR-200b和miR-4753，解除miRNA对SOX2的作用，或/和直接结合SRC调控SOX2的表达，进而促进三阴乳腺癌生长与转移。本项目拟采用CRISPR/Cas9和动物成像等技术阐明crEPSTI1上、下游分子的调控机制，为三阴乳腺癌生长与转移的研究提供新的理论依据和治疗靶点。

Recent studies have shown that circular RNA could regulate microRNAs and gene expression, which is closely related with the occurrence and development of cancers. We previously confirmed that miR-200b could inhibit the growth and metastasis of triple negative breast cancer. Through a high-throughput circular RNA microarray and preliminary experiment，we found that CircRNA-crEPSTI1 was highly expressed in triple negative breast cancer cell lines and tissues. Meanwhile, its high expression was positively correlated with lymph node metastasis and prognosis. The functional experiment results showed that overexpression of crEPSTI1 could down regulate miR-200b and miR-4753 and promoted the proliferation and invasion of triple-negative breast cancer. Bioinformatics predicts that both miR-200b and miR-4753 can target SOX2. Further experiments revealed that crEPSTI1 could also bind to oncogene SRC, which can promote the expression of SOX2. Therefore, we propose a scientific hypothesis that to promote the growth and metastasis of triple negative breast cancer, crEPSTI1 rescuer the inhibition of SOX2 by absorbing miR-200b and miR-4753, and/or regulate the expression of SOX2 by direct binding to SRC. In this project, CRISPR / Cas9 and animal imaging techniques will be used to elucidate the mechanism. Ultimately, this project could provide a new theoretical basis for pathogenesis researches and new therapeutic targets for triple negative breast cancer.