环状RNA hsa_circ_0005785作为新的肝癌生物标志物及其作用机制研究

环状RNA在肿瘤发生发展过程中起重要作用，我们前期发现hsa_circ_0005785在肝细胞肝癌（HCC）中高表达，与增殖诱导配体（APRIL）表达呈正相关，促进HCC生长转移。根据预实验结果，推测hsa_circ_0005785可通过竞争结合miR-383，促进HCC细胞表达分泌APRIL；还可通过绑定趋化因子CXCL5，增强其趋化能力，促使肿瘤相关中性粒细胞浸润并释放APRIL。自分泌和旁分泌的APRIL进一步激活NF-κB通路，增强CXCL5基因转录，二者形成正反馈环路，加速HCC进展。本项目旨在解析hsa_circ_0005785通过充当“miRNA海绵”及参与“中性粒-肿瘤交互对话”促进HCC恶性进展的分子机制。同时，建立并评价qPCR法检测血浆hsa_circ_0005785含量，探讨其作为新的HCC生物标志物的临床应用价值。本研究有望为HCC基础与临床研究提供新思路和靶标。

Circular RNA plays an important role in the occurrence and development of the malignancies. Our previous studies have found that hsa_circ_0005785 is highly expressed in hepatocellular carcinoma (HCC) and has a positive correlation with the expression of a proliferation-inducing ligand (APRIL). Both of them can promote HCC growth and metastasis. According to the results of preliminary experiments, we speculate that hsa_circ_0005785 can competitively combine with miR-383 to facilitate APRIL expression in HCC. On the other hand, HCC cells can recruit tumor-associated neutrophils (TANs) which release APRIL through hsa_circ_0005785 binding chemotactic factor CXCL5. Furthermore, APRIL, derived from autocrine and paracrine, activates the NF-kappa B signaling pathway and enhances CXCL5 gene transcription. Both of them form a positive feedback regulatory loop to accelerate the progress of HCC. Accordingly, the aim of this project is to explore the molecular mechanisms of hsa_circ_0005785 acting as a “miRNA sponge” and participating in the "neutrophils-tumor interaction dialogue" to promote the malignant progress of HCC. In addition, a qPCR method to detect plasma hsa_circ_0005785 will be established and its methodology will also be evaluated in order to explore its clinical application values as a promising biomarker for HCC. Thus, our study might provide a novel idea and target for study of the pathogenesis, as well as clinical diagnosis and treatment of HCC.