外泌体介导circFLT3调控肿瘤-骨微环境在骨巨细胞瘤进展和骨破坏中的作用和机制研究

骨巨细胞瘤（GCTB）是最常见的骨原发侵袭性肿瘤之一，溶骨破坏是其最特征的表现。外泌体及环状RNA均被证实在肿瘤发展和肿瘤微环境中发挥重要作用，但外泌体或环状RNA在GCTB中均尚未有研究报道。项目组的前期研究发现GCTB患者肿瘤完全切除后血浆外泌体中circFLT3（circ0100160）的水平显著下降，且circFLT3可能通过结合miR-377和miR-188-3p促进骨巨细胞瘤基质细胞增殖和破骨细胞分化，而外泌体介导的circFLT3可显著促进单核细胞向破骨细胞的分化，说明外泌体介导的circFLT3可能在GCTB肿瘤-骨微环境中发挥重要作用。基于这些研究结果，项目组拟明确血浆外泌体中circFLT3对GCTB复发、药物疗效及预后等的评估作用，并进一步在分子、细胞和在体水平阐明外泌体介导circFLT3在GCTB进展和骨破坏中的作用和机制，为GCTB的临床诊断和治疗提供新的靶点。

Giant cell tumor of bone (GCTB) is one of the most common primary aggressive bone tumor, which is labeled by severe osteolytic destruction. Both exosomes and circular RNA (circRNA) have been reported to play important roles in tumor development and microenvironment. However, neither exosome nor circRNA has been reported in GCTB. Our previous studies firstly showed that the level of circFLT3 (circ0100160) in plasma exosomes significantly decreased in GCTB patients underwent en-bloc resection of the tumor. Furthermore, we found that circFLT3 might promote the proliferation of giant cell tumor stromal cells (GCTSCs) and the osteoclast differentiation induced by GCTSCs through binding to miR-377 and miR-188-3p. In addition, exosomal circFLT3 could also promote the differentiation of monocytes into osteoclasts. These results suggest that circFLT3 and exosomal circFLT3 may play important roles in tumor-bone microenvironments of GCTB. Next, we intend to detect the role of circFLT3 in the evaluation of GCTB recurrence, drug efficacy and prognosis, and further elucidate the role and mechanism of circFLT3 mediated by exosomes in the progress of GCTB and bone destruction both in vitro and in vivo. The present study may provide a new target for the clinical diagnosis and treatment of GCTB.