CXCR7/CXCR4异二聚体促进结直肠癌发生与发展的作用目前已被证实，调控过程可能与组蛋白去甲基化有关，但是具体分子机制还不清楚。前期发现CXCR7/CXCR4被激活后可诱导βarr1入核，增强组蛋白去甲基化酶JMJD2A的转录。假设核内βarr1引导转录因子KLF8及组蛋白乙酰转移酶p300到JMJD2A启动子上并形成βarr1/KLF8/p300复合物，激活JMJD2A转录，最终导致C-Myc等基因上组蛋白去甲基化。拟使用临床样本和小鼠结直肠癌模型，结合体外实验，分析βarr1/KLF8/p300参与CXCR7/CXCR4诱导的结直肠癌发生发展及免疫逃逸的过程；利用CRISPR敲除βarr1、KLF8、p300活性以阻断βarr1/KLF8/p300的形成，并以Co-IP、ChIP、荧光素酶报告基因等分析其调控JMJD2A的分子机制，为结直肠癌的防治提供新思路和理论依据。

The role of CXCR7/CXCR4 heterodimer in promoting the occurrence and development of colorectal cancer has been confirmed. The regulatory process may be related to histone demethylation, but the specific molecular mechanism is still unclear. It was found that CXCR7/CXCR4 heterodimer was activated to induce βarr1 to enter the nucleus and enhance the transcription of histone demethylase JMJD2A. We suppose that the nuclear βarr1 guides the transcription factor KLF8 and histone acetyltransferase p300 to the JMJD2A promoter to form a βarr1/KLF8/p300 complex, activating JMJD2A transcription, which ultimately leads to the demethylation of histones at C-Myc and other genes. It is planned to use clinical samples and mouse colorectal cancer models, combined with in vitro experiments, to analyze the process of βarr1/KLF8/p300 participating in the development and immune escape of colorectal cancer induced CXCR7/CXCR4 heterodimer; We use CRISPR to knock out βarr1, KLF8, p300 activity to block the formation of βarr1/KLF8/p300, and analyze the Molecular mechanism of regulation of JMJD2A by Co-IP, ChIP, luciferase reporter gene assay, etc., which provide for the prevention and treatment of colorectal cancer New ideas and theoretical basis.