胶质瘤中乏氧微环境介导的HIF-1α/miR-24/CCL-2通路调控巨噬细胞招募的机制研究

It is well known that tumor associated macrophages were existed in the hypoxia region of glioma. However, the mechanism remains unknown. Our data shows that hypoxia mediated HIF-1α induces the expression of miR-24. Downregulation of miR-24 suppressed macrophages recruition as well as CCL-2 which is one of the famous chemokines. Thus, we proposed that hypoxia mediated HIF-1α/miR-24/CCL-2 pathway regulate macrophages recruitment in glioma. In the future study, we will construct glioma cells with different status of miR-24 as cell models and transcriptional and posttranscriptional regulation as major methods, evalute the effect of HIF-1α mediated by hypoxia on miR-24 transcription and the function of miR-24/CCL-2 pathway on macrophages recruition. Further analyze the key notes in glioma molecular dignosis and prognosis. In conclusion, our finding may reveal a novel mechanism of macrophages recruiting in glioma, and provide more potential approaches for glioma microenviroment target therapy.

研究证实胶质瘤乏氧区域存在大量肿瘤相关巨噬细胞，有关具体机制尚未明确。课题组前期发现：乏氧介导的HIF-1α上调胶质瘤miR-24表达；下调胶质瘤miR-24抑制趋化因子CCL-2表达及巨噬细胞招募。据此，我们提出科学假设“胶质瘤中乏氧微环境介导HIF-1α/miR-24/CCL-2通路调控肿瘤相关巨噬细胞招募的机制研究”。本课题拟以miR-24不同状态脑胶质瘤细胞为模型，通过转录调控、转录后抑制层面，全面分析乏氧微环境介导的HIF-1α对miR-24的转录调控；miR-24/CCL-2通路对胶质瘤相关巨噬细胞招募及其功能的影响；阐释此通路中关键节点在胶质瘤分子诊断及预后判断中的作用。本课题将揭示胶质瘤微环境中肿瘤相关巨噬细胞招募的新机制，为针对胶质瘤微环境靶向治疗提供新思路。

 研究证实胶质瘤乏氧区域存在大量肿瘤相关巨噬细胞，有关具体机制尚未明确。课题组前 期发现：乏氧介导的HIF-1α上调胶质瘤miR-24表达；下调胶质瘤miR-24抑制趋化因子CCL-2表 达及巨噬细胞招募。据此，我们提出科学假设“胶质瘤中乏氧微环境介导HIF-1α/miR-24/CCL -2通路调控肿瘤相关巨噬细胞招募的机制研究”。本课题拟以miR-24不同状态脑胶质瘤细胞为 模型，通过转录调控、转录后抑制层面，全面分析乏氧微环境介导的HIF-1α对miR-24的转录 调控；miR-24/CCL-2通路对胶质瘤相关巨噬细胞招募及其功能的影响；阐释此通路中关键节点 在胶质瘤分子诊断及预后判断中的作用。本课题将揭示胶质瘤微环境中肿瘤相关巨噬细胞招募 的新机制，为针对胶质瘤微环境靶向治疗提供新思路。