环状RNA circADAMTS13/miRNA/ADAMTS13信号轴在肝癌发生发展中的分子机制研究

ADAMTS13是一种具有血小板反应蛋白1型基序的金属蛋白酶，可抑制肝癌的血管新生，但其上游调控机制目前仍不清楚。我们前期基于高通量测序技术筛选了肝癌发生发展相关的circRNAs并进行表达验证及功能研究，发现circADAMTS13在肝癌组织中低表达，且与肝癌细胞的增殖及血管生成相关。进一步分析发现其可调控其亲本基因ADAMTS13的表达，但作用机制仍有待探讨。本项目拟以circADAMTS13/miRNA/ADAMTS13信号轴为出发点，研究三者间的互作机制及在炎症诱导下circADAMTS13介导肝癌血管新生的分子机制；另外，本项目还将探讨circADAMTS13与ADAMTS13在肝癌组织中表达的相关性及其与肝癌临床特征的关系。本项目的研究将阐明circADAMTS13调控肝癌发生发展的分子机制，为其作为诊断和治疗的潜在靶标提供理论依据。

ADAMTS13, a thrombospondin-1-type metalloprotease,could inhibit angiogenesis in hepatocellular carcinoma, but its up-regulation mechanism remains unclear. Our preliminary studies have identified specific circRNAs with potential roles in HCC development based on high-throughput sequencing technology. Expression spectrum and functional analysis revealed that one specific circRNA, defined as circADAMTS13, significantly lower expressed in HCC tissue and its overexpression in HCC cell lines could significantly inhibit cell proliferation and angiogenesis. Further studies indicated that circADAMTS13 could regulate the expression of its parental gene ADAMTS13, while the exact molecular mechanisms remained to be further explored. In this study, we will focus on circADAMTS13 / miRNA / ADAMTS13 signal axis, and further investigate the mechanism of circADAMTS13 inhibiting angiogenesis of HCC under inflammation induction. In addition, we will analyze the correlations between the expression of circADAMTS13 and ADAMTS13 in HCC tissues, and further explore their correlations with the clinical characteristics. This study will elucidate the molecular mechanisms of circADAMTS13 in hepatocarcinogenesis, and provide fundamental data and knowledges for applying the circADAMTS13 as a potential diagnostic and therapeutic target.