结直肠癌干细胞（CRC-SC）与结直肠癌（CRC）增殖转移和化疗耐药密切相关，逆转CRC-SC干性是治疗CRC重要途径。本项目组前期研究新发现miR-506具有干性调控作用，能够通过BMP-4逆转CRC-SC干性，并发现miR-506对BMP-4调控是通过靶向EZH2实现。项目组在上述发现基础上拟深入研究：一是在CRC-SC中验证miR-506具有干性调控功能。二是验证miR-506通过BMP-4调控CRC-SC干性，同时验证miR-506通过EZH2调控BMP-4，并从DNA和组蛋白甲基化角度研究EZH2调控BMP-4机制。三是构建裸鼠移植瘤模型，验证miR-506在体内能够逆转CRC-SC干性及机制。四是检测CRC组织中相关分子表达水平，并进行相关性分析。本项目期望探明miRNA-506在CRC-SC干性逆转中的作用和机制，为治疗CRC提供新思路、新靶点。

Colorectal cancer stem cells (CRC-SC) are closely associated with proliferation, metastasis and chemotherapy resistance of colorectal cancer (CRC), reversing CRC-SC stemness is an important way to treat CRC. Our previous research newly discovered that miR-506 function as stemness regulator, which can reverse CRC-SC stemness by BMP-4, and it was also found that miR-506 regulating BMP-4 was achieved by targeting EZH2. The project should be further studied on the basis of the above findings: Firstly, verifying that miR-506 function as stemness regulator in the CRC-SC. Secondly, verifying that miR-506 regulates CRC-SC stemness through BMP-4, and verifyies that miR-506 regulates BMP-4 through EZH2, and studing the mechanism ragarding EZH2 regulating BMP-4 from aspects of DNA and histone methylation. Thirdly, we constructed nude mice transplanted tumor model to verifying that miR-506 could reverse CRC-SC stemness in vivo and study its mechanism. Fourthly, the expression of related molecules in CRC tissue were detected and the correlation of these molecules were analyzed. This project is expected to explore the role and mechanism of miRNA-506 in CRC-SC stemness reversal and provide new ideas and strategies for the treatment of CRC.