骨肉瘤细胞凋亡机制研究对于认识骨肉瘤发生发展过程及化疗抵抗的原因均具有重要价值。我们前期研究发现骨肉瘤中凋亡相关的miR-133a显著下调，但是其下调机制尚不清楚。芯片筛选发现骨肉瘤组织中LDLRAP1基因与miR-133a呈现良好负相关，且LDLRAP13’非翻译区（UTR）含有4个miR-133a结合位点，过表达LDLRAP1 3’UTR可以显著降低miR-133a水平。因此我们设想，LDLRAP1可能通过3’UTR发挥miR-133a海绵作用抑制骨肉瘤细胞凋亡。本项目拟在体外细胞和动物模型上系统研究LDLRAP1非编码区对骨肉瘤增殖和抵抗凋亡作用的调控意义，验证其作用是否依赖于miR-133a海绵机制；并结合临床样本分析LDLRAP1对于骨肉瘤耐药形成的意义和药敏预测价值，从而深入探讨骨肉瘤凋亡抵抗和耐药形成的分子机制，为耐药性骨肉瘤的诊疗提供新的有转化前景的研究靶点。

Studies on the osteosarcoma cells apoptosis regulation are important to understand the mechanism for osteosarcoma development and its resistance to chemotherapy. Our previous studies found that miR-133 was down-regulated in osteosarcoma tissues, and miR-133 can increase osteosarcoma cells apoptosis resistance, but the underlying mechanisms remain undefined. Basing on a microarray analysis, we also found LDLRAP1 was elevated in osteosarcoma tissues, and there are 4 miR-133a binding sites on LDLRAP1’s 3’UTR, which can induced a decrease of miR-133a levels in osteosarcoma cells.Therefore, our current study aims to explore whether LDLRAP1’s 3’UTR can suppress osteosarcoma cells apoptosis as an endogenous miR-133a sponges. Further studies include the in vitro analysis of the functions of LDLRAP1’s 3’UTR as miR-133 sponges to regulate osteosarcoma cells apoptosis, and the role of this function on the mechanism of osteosarcoma chemotherapy resistance. Our plan may add new knowledge to the mechiansm of osteosarcoma apoptosis resistance and may provide some new targets or strategy for osteosarcoma therapy studies.