PRL-3-miR-103a-Runx2通路在骨肉瘤转移中的功能及机制研究

Osteosarcoma (OS) is a kind of malignant tumor which often occurred in children and teenager. The metastasis of OS has made the treatment harder and survival rate lower. Our group previously found that PRL3 is enhanced in patients with OS, which can be involved in the invasion and migration of osteosarcoma cells. But the pathogenesis was still unknown. This subject intends to investigate the function and mechanism of PRL3-miR-103a-Runx2 pathway by using adenovirus infection, transfection, dual-luciferase reporter gene assay, Chip assay and RNAi technologies, in the invasion and migration of osteosarcoma cells. This study not only can clarify that the PRL3-miR-103a-Runx2 pathway is play an important role in the metastasis of OS preliminarily, but also can create a new explanation of the mechanism of OS metastasis, and the new target of OS treatment will can be discovered too.

骨肉瘤(OS)是儿童和青少年最常见的恶性肿瘤之一，骨肉瘤转移增加了其治疗难度，使五年生存率大幅下降。我们课题组前期发现：PRL3在骨肉瘤中高表达，并与骨肉瘤患者的生存率成负相关，与肺转移呈正相关；直接参与了骨肉瘤细胞的侵袭、迁移。但相关的分子机制尚不清楚。miR-103a-Runx2是我们筛选得到的受PRL3调控的关键分子，在PRL3促进骨肉瘤侵袭、转移的进程中发挥了重要作用。本课题拟在前期工作基础上，以PRL3-miR-103a-Runx2通路的功能及其调控机制研究为突破口，综合利用慢病毒感染、报告基因、RNAi等分子生物学技术，系统研究PRL3-miR-103a-Runx2通路在骨肉瘤细胞侵袭、迁移过程中发挥的作用及其调控机制，为骨肉瘤转移的机制研究提供新的认识，为临床骨肉瘤转移的防治提供潜在的药物作用靶点。

骨肉瘤(OS)是儿童和青少年最常见的恶性肿瘤之一，骨肉瘤转移增加了其治疗难度，使五年生存率大幅下降。我们课题组前期发现：PRL3在骨肉瘤中高表达，并与骨肉瘤患者的生存率成负相关，与肺转移呈正相关；直接参与了骨肉瘤细胞的侵袭、迁移。本课题在前期工作基础上，以PRL3-miR-103a-Runx2通路的功能及其调控机制研究为突破口，完善了 PRL3 与临床肿瘤组织病理分型、分期的相关性研究；明确了PRL3表达与骨肉瘤患者不良预后的相关性；构建了裸鼠胫骨髓腔原位荷瘤模型，初步评价了PRL-3在裸鼠胫骨髓腔原位荷瘤模型中的功能；恢复性实验证实了PRL-3通过miR-103a对骨肉瘤细胞生物学功能的影响。系统研究PRL3-miR-103a-Runx2通路在骨肉瘤细胞侵袭、迁移过程中发挥的作用及其调控机制，为骨肉瘤转移的机制研究提供新的认识，为临床骨肉瘤转移的防治提供潜在的药物作用靶点。