多年来索拉非尼始终是晚期肝癌一线治疗药物，但其耐药问题一直是限制疗效的 “瓶颈”。我们前期研究发现miR-210-5p在肝癌中高表达并与索拉非尼耐药和乏氧调节密切相关，SPON2是miR-210-5p负调控的靶基因。结合国内外研究报道，推测miR-210-5p调控靶基因SPON2可能介导肝癌M2型肿瘤相关巨噬细胞（M2-TAM）极化参与诱导索拉非尼耐药。因此，本课题拟从分子、细胞、组织及实验动物水平，探索缺氧条件下miR-210-5p调控SPON2介导肝癌M2-TAM极化的分子机制；通过生物信息学方法和IPA互作网络，结合动物实验与临床样本回归性分析，筛选并验证M2-TAM极化参与索拉非尼耐药的信号通路，旨在阐明miR-210-5p调控SPON2介导肝癌M2-TAM极化参与索拉非尼耐药的作用机制，有望为干预或改造M2-TAM极化提供新的策略，为进一步提高肝癌的疗效提供潜在分子靶点。

The anti-angiogenic drugs represented by sorafenib over the years have always been the first-line treatment of advanced liver cancer, but the drug resistance problem has always been a "bottleneck" in curative effect. Our previous study found that miR-210-5p is highly expressed in hepatocellular carcinoma and is closely related to sorafenib resistance. Combined with domestic and foreign research reports, we speculated that miR-210-5p might target to SPON2 to the polarization of M2-TAM in the induction of sorafenib resistance in HCC. Therefore, the mechanism of miR-210-5p targeted SPON2-mediated polarization of M2-TAM cell in hepatocellular carcinoma will be assessed and studied. The bioinformatics analysis method and IPA interaction network were used to screen and validate the polarization of M2-TAM cells involved in sorafenib resistance signaling pathway by combining the regression analysis of animal experiments and clinical samples. In all, it’s important to perform this study, thus providing a new strategy for intervention or modification of M2-polarization of TAM in hepatocellular carcinoma efficacy of anti-angiogenic drugs in the treatment of liver cancer.