选择性剪接在基因组中广泛存在，越来越多的研究显示,与肿瘤发生发展密切相关的癌基因、抑癌基因、肿瘤转移基因等均可发生选择性剪接，从而影响肿瘤进程。骨桥蛋白（Osteopontin,OPN）是一种分泌型的磷酸化糖蛋白，参与多种恶性肿瘤的发生和转移。人OPN通过选择性剪接产生三种剪切体，其功能与机制尚不清楚。我们前期研究发现OPN在肝癌侵袭转移中发挥重要作用，可作为预后指标和干预靶点，并初步发现三种剪接体在肝癌的发生发展中可能扮演不同的角色。本项目拟在前期研究的基础上，系统解析肝癌侵袭转移过程中OPN选择性剪接产生的三种剪接体的动态变化规律及其功能差异，绘制三种剪接体蛋白作用网络，揭示不同剪接体调控上皮间质转分化(EMT)进而影响肝癌转移的分子机制。本课题的研究对进一步阐明OPN在肿瘤转移复发中的重要功能奠定基础，同时为肝癌转移复发的分子分型预测和干预提供强有力的证据。

Alternative splicing of genes is essential for regulating gene expression and contributing to functional complexity.Osteopontin (OPN), a secreted phosphoglycoprotein, is a promoting factor for tumorigenicity and metastasis of cancer cells in several types of tumors through a variety of mechanisms. Our previous studies demonstrated that OPN played a crucial role in hepatocellular carcinoma (HCC) metastasis. In HCC, increased OPN levels are associated with metastasis, poor prognosis, and early tumor recurrence. Three OPN isoforms (OPN-a, -b and -c) derived from alternative splicing are known to exist, but their functional specificity on HCC metastasis and prognosis is not clear yet and deserves further investigation. Based on the present study, we further construct the expression profile of OPN isoforms in HCC correlated with specific cellular phenotypes and tumorigenicity of HCC and research the molecular interation between proteins with OPN isoforms using molecular biology techniques such as Co-IP, et al. It would be great help for the molecular prediction of metastases, recurrence, and prognosis in hepatocellular carcinoma.