外泌体源性circRNA是极有临床应用潜力的肿瘤诊断标志物和分子靶点。前期发现：miR-370/UBQLN4轴通过调控Wnt/β-catenin通路参与肝癌进展；生信分析及预实验提示环状RNA circ-0003141竞争性结合miR-370调控UBQLN4表达，增强肝癌恶性表型；外泌体源性circ-0003141和肝癌恶性表型相关，且能激活Wnt/β-catenin通路。据此提出假说：外泌体源性circ-0003141通过调控miR-370/UBQLN4轴激活Wnt/β-catenin通路，促进肝癌进展。本课题拟从组织样本、细胞、动物三个层次阐明circ-0003141调控miR-370/UBQLN4轴的分子机制；揭示circ-0003141/miR-370/UBQLN4信号轴对肝癌恶性表型的影响；明确外泌体源性circ-0003141的临床意义及生物学功能，为肝癌诊疗提供新思路和新策略

Exosomal circRNA may serve as a potential diagnostic marker or target for cancer treatment. We previously found that miR-370/UBQLN4 axis contributed to HCC progression through activating Wnt/β-catenin pathway. Bioinformatics analysis and experimental verification indicated that circRNA circ-0003141 could regulated UBQLN4 expression through acting as a sponge of miR-370. Moreover, knockdown of circ-0003141 suppressed the malignant biological behaviors of HCC cells. Furthermore, expression of exosomal circ-0003141 was associated with the clinical prognosis. Exosomal circ-0003141 could activated Wnt/β-catenin pathway. Hence, we speculated that the exosomal circ-0003141 promote HCC progression via the miR-370-UBQLN4 axis mediated Wnt/β-catenin activation. In this study, via clinical tissue specimens, cell experiments and mice tumor-burdened model, we aim to illustrate the molecular mechanism of circ-003141/miR-370/UBQLN4 network. We also explored the functional role of circ-003141/miR-370/UBQLN4 axis in promoting malignant phenotype of HCC, and ascertain the biological function of exosomal circ-0003141 in HCC. These findings will provide novel targeting strategies for the treatment of HCC.