TACE术后肝癌细胞外泌体circ_0084615促进肝癌肺转移的机制研究

Transcatheter arterial chemoembolization (TACE) is the effective treatment for inoperable hepatocellular carcinoma (hereinafter referred to as HCC). However, the recurrence and metastasis of HCC after TACE treatment is still the main problem. Numerous studies suggest that communication between tumor cells and tumor microenvironment mediated by exosomes promotes the development of tumor. This study found that the expression of circ_0084615 in exosomes from HCC cells treated with TACE was upregulated. circ_0084615 expression is correlated with lung metastasis. Exosomal circ_0084615 from HCC cells can be ingested by HUVECs to promote its proliferation and migration. circ_0084615/AUF1/KLF2/VEGFR2, occludin control axis may exist in HUVECs. Therefore, this study aims to explore the underlying mechanism of higher expression of circ_0084615 from HCC exosomes after TACE and the mechanism of circ_0084615 regulating pulmonaty vascular infiltration and angiogenesis. We aim to elucidate the mechanism of circ_0084615 regurating the formation of lung microenvironment before metastasis and promote lung metastasis of HCC after TACE, and thus provide new theoretical basis and direction for treatment of HCC.

肝动脉化疗栓塞（TACE）是不可切除肝细胞性肝癌（下称肝癌）患者的有效治疗手段，TACE术后肝癌复发和转移仍是其面临的主要问题。大量研究表明外泌体介导的肿瘤与微环境交流促进了肿瘤进展。本研究发现肝癌患者TACE术后血外泌体circ_0084615表达升高且其高表达与肝癌肺转移相关，肝癌外泌体circ_0084615被血管内皮细胞摄取进而促进其增殖和迁移，血管内皮细胞中可能存在circ_0084615/AUF1/KLF2/VEGFR2，occludin调控轴。因此，本课题拟探讨“TACE术后通过何种途径调控肝癌外泌体circ_0084615表达”,“circ_0084615如何调节肺血管渗透和血管生成进而促进肝癌肺转移”，以期阐明肝癌外泌体circ_0084615调节肺转移前微环境形成进而促进TACE术后肝癌肺转移的机制，为肝癌治疗提供新的理论依据和方向。

肝动脉化疗栓塞（TACE）是不可切除肝细胞性肝癌（下称肝癌）患者的有效治疗手段，TACE术后肝癌复发和转移仍是其面临的主要问题。大量研究表明外泌体介导的肿瘤与微环境交流促进了肿瘤进展。本研究发现肝癌患者TACE术后血外泌体circCAMSAP1表达升高，肝癌外泌体circCAMSAP1被血管内皮细胞摄取进而促进其增殖、迁移、血管形成及增加血管渗透，从而促进肝癌肺转移；血管内皮细胞中存在circCAMSAP1/miR-767-3p/STAT3/VEGF, occludin调控轴。本课题通过探讨TACE术后肝癌外泌体circCAMSAP1调节肺血管渗透和血管生成以期阐明肝癌外泌体circCAMSAP1调节肺转移前微环境形成进而促进TACE术后肝癌肺转移的机制，为肝癌治疗提供新的理论依据和方向。