circEPSTI1调控乳腺癌脑转移的作用及其机制研究

circRNAs are thought to be closely related with the occurrence and development of cancers. We previously confirmed that circEPSTI1 was highly expressed in tissues of brain metastatic encephaloma of breast cancer, suggested that circEPSTI1 was associated with brain metastatic of breast cancer and prognosis. The functional experiment results showed that overexpression of circEPSTI1 could down regulate miR-942 and miR-4753, and promoted the proliferation and invasion of breast cancer. Bioinformatics predicts that both miR-942 and miR-4753 can target CD47. Further experiments revealed that circEPSTI1 could also bind to oncogene c-MYC, which can promote the expression of CD47. Therefore, we propose a scientific hypothesis that to promote the brain metastasis of breast cancer, CircEPSTI1 rescuer the inhibition of CD47 by absorbing miR-942 and miR-4753, and/or regulate the expression of CD47 by direct binding to c-MYC. 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 brain metastasis of breast cancer.

环状RNA与肿瘤的发生发展密切相关。申请者前期研究结果发现：circEPSTI1在乳腺癌脑转移肿瘤组织中的表达明显高于原发瘤组织，提示circEPSTI1可能与乳腺癌脑转移相关；过表达circEPSTI1可下调乳腺癌细胞中miR-942与miR-4753的表达，促进乳腺癌细胞增殖与侵袭；生物信息学预测CD47是miR-942和miR-4753的共同靶基因。进一步研究结果发现，circEPSTI1可与c-MYC结合，文献证实c-MYC可促进CD47表达。由此，我们提出科学假说：circEPSTI1可通过吸附miR-942和miR-4753，解除miRNAs对CD47的作用，或/和直接结合c-MYC调控CD47的表达，进而促进乳腺癌发生脑转移。本项目拟采用CRISPR/Cas9和动物成像等技术阐明circEPSTI1上、下游分子的调控机制，为乳腺癌脑转移的研究提供新的理论依据和治疗靶点。

环状RNA与肿瘤的发生发展密切相关。申请者前期研究结果发现：circEPSTI1在乳腺癌脑转移肿瘤组织中的表达明显高于原发瘤组织，提示circEPSTI1可能与乳腺癌脑转移相关；过表达circEPSTI1可下调乳腺癌细胞中miR-942与miR-4753的表达，促进乳腺癌细胞增殖与侵袭；生物信息学预测CD47是miR-942和miR-4753的共同靶基因。进一步研究结果发现，circEPSTI1可与c-MYC结合，文献证实c-MYC可促进CD47表达。由此，我们提出科学假说：circEPSTI1可通过吸附miR-942和miR-4753，解除miRNAs对CD47的作用，或/和直接结合c-MYC调控CD47的表达，进而促进乳腺癌发生脑转移。本项目拟采用CRISPR/Cas9和动物成像等技术阐明circEPSTI1上、下游分子的调控机制，为乳腺癌脑转移的研究提供新的理论依据和治疗靶点。