CircCAMSAP1 promotes osteosarcoma progression and metastasis by sponging miR-145-5p and regulating FLI1 expression

Abstract Osteosarcoma is the most common primary malignant bone tumor in adolescents. While chemotherapy combined with surgery can improve the prognosis of some patients, chemo-resistance is still a huge obstacle in osteosarcoma treatment. Accumulating evidences demonstrate that circular RNAs are involved in cancer progression and metastasis, but their specific role in osteosarcoma, remains mostly undescribed. In this study, we perform circRNA deep sequencing and identify 88 distinct circRNAs from human osteosarcoma cell lines group (143B, HOS, SJSA and U2OS) and human osteoblast hFOB1.19 (control). We find that circCAMSAP1, also named hsa_circ_0004338, is significantly up-regulated in human osteosarcoma tissues and cell lines, and is positively correlates with osteosarcoma development. Silencing of circCAMSAP1 effectively suppresses osteosarcoma cell growth, apoptosis, migration, and invasion. Furthermore, we validate that circCAMSAP1 functions in osteosarcoma tumorigenesis through a circCAMSAP1/miR-145-5p/friend leukemia virus integration 1 (FLI1) pathway. FLI1 promotes osteosarcoma tumorigenesis and miR-145-5p suppresses FLI translation. CircCAMSAP1 directly sequesters miR-145-5p in the cytoplasm and inhibits its activity to suppress osteosarcoma tumorigenesis. Moreover, the regulatory role of circCAMSAP1 upregulation was examined and validated in rats. In summary, our findings provide evidence that circCAMSAP1 act as “microRNA sponge” and suggest a new therapeutic target of human osteosarcoma.