肿瘤转移是制约肝癌患者预后的主要因素。大量线索表明，肝癌患者体内异常活化的血小板能够辅助肝癌细胞远处转移。课题组前期发现，血小板内miRNAs水平变化能够影响血小板功能重塑并参与肝癌细胞免疫逃逸及血管定植。血小板作为缺乏基因组DNA的无核碎片，如何实现其内miRNAs表达水平变化？是否受到自身以外影响？目前尚无研究。基于前期基础，课题组提出：肝癌细胞分泌的miRNA可以以外泌体为载体，通过影响血小板内源性miRNA水平调控血小板功能，最终参与肝癌细胞转移。本项目拟：鉴定肝癌细胞源性miRNA并明确其与血小板作用形式；证明分泌型miRNA能够递送给血小板调控血小板功能重塑；阐明功能重塑的血小板介导肝癌细胞免疫逃逸及血管定植的分子机制。本项目完成将进一步揭示分泌型miRNA介导的“肝癌细胞-血小板”通讯机制，为建立肝癌早期监测及治疗的新策略提供思路。

Tumor metastasis is the main factor that affects the prognosis of patients with hepatocellular carcinoma. Increasing evidence suggest that the abnormal activation of platelets promotes metastasis of hepatocellular carcinoma. Recently, it is found that expression change of miRNAs in platelet affect platelet’s function, and promote immune escape and vascular colonization of HCC cells. As a fragmentation without genomic DNA, the mechanism of regulating miRNA levels in platelet is still unknown. We therefore hypothesis that platelet might receive exsomal miRNA secreted by tumor cells, and ultimately participate in the metastasis of hepatocellular carcinoma cells. In this project, to test our hypothesis, we plan to: (1) identify HCC cell derived miRNA; (2) confirm that HCC derived miRNA can be transferred to platelets and regulate platelet function; (3) investigate the role of platelet functional remodeling in immune escape and vascular colonization of HCC cells. This project will further reveal the secreting type miRNA mediated "HCC - platelet" mechanism, and provide potential biomarkers of early diagnosis and new therapeutic strategies for HCC patients.