骨肉瘤好发于青少年，恶性程度高且预后差。我们在前期研究中发现miR-125b可以通过下调STAT3抑制骨肉瘤细胞的增殖和转移；通过基因芯片分析及生物信息学预测MKK7为miR-125b调控MAPK信号通路的关键靶基因。提示miRNA-125b可能通过MAPK通路及STAT3的交互式作用抑制骨肉瘤增殖和转移。本课题拟首先检测骨肉瘤患者血清和组织中miR-125b、STAT3、MKK7表达水平，明确其与骨肉瘤的相关性；应用荧光素酶报告试验等方法阐明miR-125b通过MKK7对MAPK通路调控的分子机制，进而通过过表达及RNA干扰等技术，对STAT3、MKK7在miR-125b抑制骨肉瘤细胞增殖及转移的作用机制进行深入探讨，最终在体内进行论证，从而系统阐明STAT3、MAPK通路在miR-125b抑制骨肉瘤细胞增殖及转移过程中作用的分子机制，为骨肉瘤的临床诊断和分子靶向治疗提供新的研究靶点。

Osteosarcoma is a malignant tumor with poor prognosis, which tends to occur in adolescents and young adults. Our previous research reveals that miR-125b suppresses the proliferation and migration of osteosarcoma cells through down-regulation of STAT3. We predict MKK7 as the key target gene of miR-125b by bioinformation technique, which suggest that miR-125b can regulate MAPK pathway by targeting MKK7, and the function of miR-125b on proliferation and metastasis may be mediated through cross-communication between STAT3 and MAPK pathway. Our project intends to firstly detect miR-125b, STAT3, MKK7 expression levels in serum and tissues of patients with osteosarcoma, to confirm the correlation between them and clinical diagnosis and prognosis of osteosarcoma. Then our study will clarify the molecular mechanisms of the effect of miR-125b on MAPK pathway through targeting MKK7 by luciferase report assay, and through the over-expression and RNA interference technology, carry out a deep discussion on STAT3 and MKK7 in mechanism of miR-125b on the inhibition of cell proliferation and metastasis of osteosarcoma. At last, we check the hypothesis in vivo, in order to demonstrate proliferation and metastasis mechanism of miRNA-125b on osteosarcoma through cross-communication between STAT3 and MAPK pathway.Additionally, our research will provide a new strategy for the diagnosis and therapy for osteosarcoma.