射频消融作为肝癌主要治疗手段之一，不全消融导致残余癌的快速进展严重影响患者预后，而对其机制一直未能清楚阐明。环状RNA在不全消融残余癌的机制研究未见报道。申请者在前期工作中通过高通量测序建立了肝癌射频消融残余癌的特征非编码RNA表达谱，在差异表达的环状RNA中，circ_103595得到了临床样本的验证。并根据表达情况及碱基互补配对序列发现circ_103595可通过调控miR-185-3p来影响其靶基因PLK1的表达，从而介导肝癌的增殖。进一步分析表明细胞周期是该信号轴影响最显著的通路，故假设circ_103595/miR-185-3p/PLK1信号轴对残余癌快速增殖至关重要。本项目拟在此基础上，从临床大样本中分析总结circ_103595/miR-185-3p/PLK1信号轴与肝癌临床相关性以及对射频消融术预后判断价值。同时，在细胞和动物模型中进一步深入探讨其在残余癌中的调控作用。

Radiofrequency ablation (RFA) is one of the most essential treating strategies for liver cancer. The rapid progression of residual tumor after insufficient RFA seriously affects the prognosis of patients, and the exact mechanism is still lack of elucidation. The regulatory mechanism of circular RNAs in residual tumor has not been reported. Previously, we have established the expression profiles of noncoding RNA in residual tumor after insufficient RFA by using RNA-sequencing. Differentially expressed circular RNA circ_103595 was validated by clinical samples. We also found that circ_103595 might influence the expression of PLK1 by regulating miR-185-3p. Furthermore, close targeting correlations existed among circ_103595, miR-185-3p and PLK1, which could play an essential role in the proliferation of residual tumor. Further pathway analysis revealed that cell cycle pathway was the most significantly enriched pathway affected by circ_103595/miR-185-3p/PLK1 axis, which was essential for the rapid proliferation of residual tumor. On this basis, this project proposes to evaluate the prognostic value of circ_103595/miR-185-3p/PLK1 axis for patients with liver cancer based on a large clinical sample size. Meanwhile, based on the cell and animal models, we aim to further explore the role of circ_103595 in the proliferation and invasion of residual tumor, unraveling the effective pathways and targets in the downstream regulations.