脊索瘤是具有局部侵袭及转移能力的间叶细胞恶性骨肿瘤，对放化疗不敏感，具有极高的局部复发率和致残率。近期，越来越多的证据表明非编码RNA可参与多种肿瘤发生发展，但其在脊索瘤中的作用及机制尚不明确。我们在前期研究中证实，miR-16-5p在脊索瘤中低表达，导致下游靶基因Smad3活化，促进肿瘤发展。进一步实验显示circUSP34能够海绵吸附miR-16-5p，而过表达Smad3之后，circUSP34却表达增高。我们的假说为：脊索瘤中存在circUSP34/miR-16-5p/Smad3正反馈环路参与肿瘤的发生发展。本项目拟通过实验明确该环路的存在及其具体机制，为脊索瘤的靶向治疗提供新的靶点和思路，以期成为未来基因治疗的切入点，突破临床治疗瓶颈，提高脊索瘤的整体预后。

Chordoma is a mesenchymal malignant bone tumor with local invasion and metastasis, which is not sensitive to radiotherapy and chemotherapy and has a very high rate of local recurrence and disability. Recently, more and more evidences show that non-coding RNA can participate in the development of many tumors, but its role and mechanism in chordoma remain unclear. We confirmed in previous studies that miR-16-5p was downregulated in chordoma and target gene Smad3 was activated，finally promoting tumor development.Further experiments showed that circUSP34 was able to adsorb miR-16-5p by sponge, while overexpression of Smad3 increased the expression of circUSP34.We propose a hypothesis: the presence of circUSP34/miR-16-5p/Smad3 positive feedback loop in chordoma is involved in tumor development. This project intends to clarify the existence of the loop and its specific mechanism through experiments, and provide new targets and ideas for targeted therapy of chordoma, in order to become the entry point of future gene therapy, break through the bottleneck of clinical treatment and improve the overall chordoma Prognosis.