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 evidence demonstrates that circular RNAs (circRNAs) are involved in cancer progression and metastasis, but their specific role in osteosarcoma remains mostly undescribed. In this study, we performed circRNA deep sequencing and identified 88 distinct circRNAs from a human osteosarcoma cell lines group (143B, HOS, SJSA, and U2OS) and the human osteoblast hFOB 1.19 (control). We found that circCAMSAP1, also named hsa_circ_0004338, is significantly upregulated in human osteosarcoma tissues and cell lines, and it is positively correlated with osteosarcoma development. Silencing of circCAMSAP1 effectively suppresses osteosarcoma cell growth, apoptosis, migration, and invasion. Furthermore, we validated 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 a “microRNA sponge” and suggest a new therapeutic target of human osteosarcoma.
Highlights
Osteosarcoma (OS) is the most common form of bone cancer among adolescents and adults, with a tendency of rapid progression and a high metastatic potential.[1]
CircCAMSAP1 is relatively highly expressed in osteosarcoma tissues and cell lines and predominantly localized in cytoplasm To generate a circRNA profiling database, we performed RNA sequencing (RNA-seq) analyses of ribosomal RNA-depleted total RNA from the human osteosarcoma cell lines group (143B, HOS, SJSA, and U2OS) and the human osteoblast hFOB 1.19
We found that circCAMSAP1 was upregulated in osteosarcoma tissues and cell lines (Figures 1B and 1C)
Summary
Osteosarcoma (OS) is the most common form of bone cancer among adolescents and adults, with a tendency of rapid progression and a high metastatic potential.[1] It is reported that the 5-year survival rate of localized osteosarcoma is 69%, while for metastatic osteosarcoma the rate dropped to only 15%–30%.2,3. Every year osteosarcoma contributes to a large share of cancer-associated deaths worldwide.[4] new surgery approaches and neoadjuvant chemotherapy are widely used to treat osteosarcoma, the effectiveness of these therapies remains unsatisfied. Neither the short- or long-term survival rate of osteosarcoma has seen little change during the last three decades.
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