基于lncRNA-RIK调控巨噬细胞M2型极化在Fenretinide抗骨肉瘤转移中的作用及机制研究

骨肉瘤的高转移特性是限制患者生存的关键因素，而肿瘤相关巨噬细胞（TAM）M2型极化与肿瘤转移密切相关。靶向干预TAM的M2型极化是理想的抗骨肉瘤转移策略，但其具体机制尚不清楚。我们前期发现：抗肿瘤候选化合物Fenretinide可特异性抑制TAM的M2型极化，并发挥显著的抗骨肉瘤转移作用；同时lncRNA-chr6(lncRNA-RIK)是Fenretinide抗骨肉瘤转移的关键因子之一。基于此，我们提出假说：Fenretinide通过抑制lncRNA-RIK-STAT6信号轴，进而抑制TAM的M2型极化，最终发挥抗骨肉瘤转移的作用。在本课题，我们将进一步研究lncRNA-RIK在Fenretinide调控TAM的M2型极化及在抗骨肉瘤转移中的作用，阐明lncRNA-RIK通过介导JAK-STAT6信号通路调控TAM的M2型极化分子机制，为探索新型的抗骨肉瘤转移药物提供潜在靶点和理论依据。

High rate of metastasis is a characteristic of osteosarcoma, which limited patient survival. Tumor-associated macrophages (TAM) is reported to be involved in the metastasis of osteosarcoma cells, thus the anti-metastasis strategy by inhibition of TAM M2 type polarization has gained wide attention. However, the molecular mechanisms involved in the M2 type polarization of TAM remains elusive. Our study found that anticancer drug candidate Fenretinide could specifically inhibit TAM M2 type polarization, and display significant anti-metastasis efficacy in osteosarcoma, meanwhile lncRNA-chr6(lncRNA-RIK) is involved in this process. Based on these studies, we will further reveal the possible mechanisms underlying the anti-metastasis potential of Fenretinide by inhibition of M2 type polarization, explain how lncRNA-RIK regulated Fenretinide-suppressed M2 type polarization, and find JAK-STAT6 as the downstream targets of lncRNA-RIK. Our study not only will clarify how Fenretinide regulates M2 type polarization during osteosarcoma metastasis, but also test the feasibility of anti-metastasis treatment via M2 type polarization intervention, thus providing the potential target and theoretical basis for the design and discovery of novel anti-tumor drugs.