外泌体circ-BCAR3/miR-485/HSP90信号轴调控肝癌射频消融术后血管新生的表观遗传机制研究

"Angiogenesis" plays an important role in promoting the recurrence of "residual cancer" in hypoxic microenvironment after radiofrequency ablation (RFA) of HCC. Exosomes are vectors that have been reported in recent years to mediate this biological behavior and circular RNAs (circRNAs) play a central role. We recently established a heat shock model in vitro to simulate the microenvironment after RFA and found that exosomes significantly increase the migration ability of HUVECs. After circRNA-seq and microarray analysis of HCC, we found that circ-BCAR3 was the most highly expressed and HSP90AB1 may be the target genes of circ-BCAR3 to regulate HCC angiogenesis. Overall, this project aims to (1) further verify the effect of circ-BCAR3 on angiogenesis of HCC; (2) reveal the mechanisms of circ-BCAR3 sponging miR-485-5p to inhibit HSP90AB1; (3) use animal models to verify the effect of exosomes circ-BCAR on angiogenesis of HCC. This project is expected to reveal novel mechanisms of exosomes to regulate HCC angiogenesis after RFA and optimize clinical intervention strategies.

肝癌射频消融(RFA)术后缺氧微环境下“血管新生”是促进“残癌”复发的重要因素，外泌体(exosome)是近年报道介导这一生物学行为的媒介，而其中环状RNA(circRNA)起到核心作用。前期我们利用“热刺激”模拟RFA术后微环境，发现exosome能显著增加人脐静脉血管内皮细胞的迁移能力，肝癌外泌体CircRNA-seq测序和基因芯片分析发现了表达最为显著的Circ-BCAR3，且热休克蛋白AB1(HSP90AB1)可能是其靶基因参与血管新生。本项目拟：(1)进一步验证肝癌细胞外泌体circ-BCAR3对肝癌血管新生的作用；(2)揭示circ-BCAR3海绵吸附miR-485-5p抑制HSP90AB1的调控机制；(3)动物水平模拟RFA来验证外泌体circ-BCAR对肝癌血管新生的影响。本创新课题有望揭示exosome参与调控肝癌RFA术后血管新生的全新机制和优化临床干预策略。

肝癌射频消融(RFA)术后缺氧微环境下“血管新生”是促进“残癌”复发的重要因素，外泌体(exosome)是近年报道介导这一生物学行为的媒介，而其中环状RNA(circRNA)起到核心作用。前期我们利用“热刺激”模拟RFA术后微环境，发现exosome能显著增加人脐静脉血管内皮细胞的迁移能力，肝癌外泌体CircRNA-seq测序和基因芯片分析发现了表达最为显著的Circ-BCAR3，且热休克蛋白AB1(HSP90AB1)可能是其靶基因参与血管新生。本项目拟：(1)进一步验证肝癌细胞外泌体circ-BCAR3对肝癌血管新生的作用；(2)揭示circ-BCAR3海绵吸附miR-485-5p抑制HSP90AB1的调控机制；(3)动物水平模拟RFA来验证外泌体circ-BCAR对肝癌血管新生的影响。本创新课题有望揭示exosome参与调控肝癌RFA术后血管新生的全新机制和优化临床干预策略。