肝细胞癌（HCC）淋巴结转移（LNM）是肝外转移的主要类型之一，严重影响着患者的生存期和生活质量，其发生机制研究对HCC LNM的精准治疗十分关键。前期研究发现环状RNA-0044539与miRNA-29a有吸附关系且均与HCC LNM相关，VEGFA是miRNA-29a的靶基因，miRNA-29a可富集于肿瘤外泌体，HIF-1α和CXCR4在HCC中高表达且均和LNM有关，HIF-1α促进外泌体释放。据此假设：环状RNA-0044539通过miRNA-29a调控VEGFA及下游通路上调CXCR4；并经外泌体促进髓源性抑制细胞功能，抑制淋巴结肿瘤免疫，协同促进HCC LNM。本研究拟从分子、细胞和整体水平，利用病理标本、肝癌细胞和HCC LNM模型，以原位杂交、基因敲减、荧光标记外泌体动态显像等方法验证假设，阐明HCC LNM的机制，为HCC LNM高危患者的精准治疗提供理论依据和新思路。

Hepatocellular carcinoma (HCC) lymph node metastasis (LNM) is one of the main types of extrahepatic metastasis, which seriously affects the survival of patients. The relevant mechanism research is critical for the precision treatment of HCC LNM. Our previous studies have found that circRNA-0044539 functions as a sponge of miRNA-29a and both are correlated with HCC LNM. VEGFA is the target gene of miRNA-29a, miRNA-29a can be enriched in tumor exosomes. The high expression of HIF-1α and CXCR4 in HCC is related to LNM. Simultaneously, high expression of HIF-1α up-regulated the release of exosomes. Accordingly, we hypothesized that circRNA-0044539 up-regulates the expression of CXCR4 through the regulation of VEGFA and downstream pathway by microRNA-29a, and promotes the function of myeloid-derived suppressor cells (MDSCs) through exosomes to mediate tumor immunosuppression in lymph node, which synergistically facilitate HCC LNM. Based on pathological specimens, HCC cells and HCC LNM models, we intend to validate the hypothesis and clarify the molecular mechanism of HCC LNM using in situ hybridization, gene knock-down, fluorescent labeled exosomes dynamic imaging, etc. from molecular, cellular and overall levels. It may provide theoretical bases and new ideas to achieve precision treatment for high-risk patients with HCC LNM.