BMI1通过miR-146a/NF-κB信号轴调控炎症相关结直肠癌进展的机制研究

结直肠癌（CRC）是胃肠道中常见的恶性肿瘤，肿瘤微环境特别是肿瘤相关巨噬细胞（TAMs）对结直肠癌发生发展至关重要，但TAMs对结直肠癌的作用机制还不是很清楚。我们前期研究发现，TAMs中Bmi1的缺失能抑制炎症相关结直肠癌（CAC）的进展，且初步发现是通过调控miR-146a/NF-κB信号轴来实现的。本项目将在此研究基础上，进一步明确Bmi1在TAMs中的缺失对CAC肿瘤发生发展的影响，揭示BMI1调控miR-146a表达的具体作用机制，阐明BMI1/miR-146a/NF-κB信号轴调控CAC进展的分子机制。本项目的实施将为更全面的诠释BMI1功能提供新的理论依据，也为TAMs的促癌功能提供新的认识，对肠道肿瘤的治疗提供新的线索。

Colorectal cancer (CRC) is the most common cancer of the gastrointestinal tract. Tumor microenvironment, especially the tumor-associated macrophages (TAMs), is a known crucial factor for CRC tumorigenesis, yet the underlying molecular mechanism have not been comprehensively deciphered. Our preliminary studies have shown that deletion of Bmi1 in TAMs was able to significantly inhibit tumor initiation and development in the colitis-associated cancer (CAC), and preliminary verified that this function may be achieved through the regulation of miR-146a/NF-κB signaling axis. On the basis of these data, we will further investigate the regulatory role of BMI1 in colitis-associated tumorigenesis, reveal the molecular mechanism of BMI1 regulates miR-146a expression, and elucidate the underlying mechanism of BMI1/miR-146a/NF-κB signaling axis in the regulation of colorectal tumor. We believe this project will lead to a better understanding of properties and regulatory mechanisms of BMI1, also providing new insight to TAMs function and novel approach to treatment of colorectal cancer.