低氧微环境对肝细胞癌的发生发展具有重要影响，巨噬细胞M2型极化在肝癌的中晚期转移中发挥重要作用，但关于肝癌细胞在低氧环境下调控巨噬细胞极化的机制尚不完全清楚。我们前期研究发现，低氧能够诱导肝癌细胞外泌体的分泌，并且外泌体miR-362-3p具有调控巨噬细胞M2型极化的作用。因此，结合前期研究结果，我们提出假说：低氧能够通过调控Rab10促进肝癌细胞外泌体的分泌；外泌体在hnRNPA1的作用下选择性运载miR-362-3p进入巨噬细胞；外泌体miR-362-3p通过靶向调控SOCS3/STAT3信号转导通路促进巨噬细胞M2型极化。本项目拟应用临床标本、体外细胞实验和动物模型，通过ChIP、EMSA、RIP、RNA pull-down、荧光素酶报告基因等实验技术，研究肝癌细胞低氧外泌体miR-362-3p介导调控巨噬细胞M2型极化的分子机制，为肝癌的靶向微环境治疗提供新的方向。

Hypoxic microenvironment has an important impact on the occurrence and development of hepatocellular carcinoma (HCC). Macrophages M2 polarization plays an important role in the metastasis of middle and advanced stages of HCC. However, the mechanism by which HCC cells regulate macrophage polarization in the hypoxic microenvironment is not clear. Our previous research found that hypoxia could induce exosomes secretion in HCC cells, and exosomal miR-362-3p could mediate the regulation of macrophages M2 polarization. Therefore, based on the results of previous studies, we hypothesis that hypoxia can promote the exosomes secretion in HCC cells by regulating Rab10; exosomes selectively deliver miR-362-3p into macrophages via the function of hnRNPA1; exosomal miR-362-3p induces the M2 polarization of macrophages by targeting regulation of SOCS3/STAT3 signaling pathway. In this study, we will utilize clinical tissue specimens, cell experiments and animal models, as well as ChIP, EMSA, RIP, RNA pull-down, luciferase report gene and other experimental technologies to study the molecular mechanisms of hypoxic exosomal miR-362-3p derived from HCC cells mediates M2 polarization of macrophages and provide a new direction for targeted microenvironment therapy of HCC.