circCAMSAP1 promotes osteosarcoma progression and metastasis by sponging miR-145-5p and regulating FLI1 expression.
circCAMSAP1 promotes osteosarcoma progression and metastasis by sponging miR-145-5p and regulating FLI1 expression.
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circCAMSAP1通过海绵miR-145-5p和调节FLI1表达促进骨肉瘤进展和转移
DOI：
10.1016/j.omtn.2020.12.013
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发表时间：
2021-03-05
期刊：
影响因子：
--
通讯作者：
Fan S
中科院分区：
文献类型：
--
作者：
Chen Z;Xu W;Zhang D;Chu J;Shen S;Ma Y;Wang Q;Liu G;Yao T;Huang Y;Ye H;Wang J;Ma J;Fan S
骨肉瘤是青少年最常见的原发性恶性骨肿瘤。化疗联合手术治疗可改善部分患者的预后，但化疗耐药仍是骨肉瘤治疗的一大障碍。越来越多的证据表明，环状RNA（circRNA）参与癌症的进展和转移，但其在骨肉瘤中的具体作用仍然是大多数未描述。在这项研究中，我们进行了circRNA深度测序，并从人骨肉瘤细胞系组（143 B，HOS，SJSA和U2 OS）和人成骨细胞hFOB 1.19（对照）中鉴定了88种不同的circRNA。我们发现，circCAMSAP 1，也称为hsa_circ_0004338，在人骨肉瘤组织和细胞系中显著上调，并且与骨肉瘤的发展呈正相关。circCAMSAP 1沉默有效抑制骨肉瘤细胞生长、凋亡、迁移和侵袭。此外，我们验证了circCAMSAP 1通过circCAMSAP 1/miR-145- 5 p/friend白血病病毒整合1（FLI 1）途径在骨肉瘤肿瘤发生中发挥作用。FLI 1促进骨肉瘤肿瘤发生，miR-145- 5 p抑制FLI翻译。circCAMSAP 1直接在细胞质中螯合miR-145- 5 p并抑制其抑制骨肉瘤肿瘤发生的活性。此外，在大鼠中检查并验证了circCAMSAP 1上调的调节作用。总之，我们的研究结果提供了证据表明，circCAMSAP 1作为一个“microRNA海绵”，并提出了一个新的治疗靶点的人骨肉瘤。骨肉瘤是青少年最常见的原发性恶性骨肿瘤。本研究旨在探讨环状RNA circCAMSAP 1在骨肉瘤中的作用及其机制。我们表明circCAMSAP 1与骨肉瘤肿瘤发生正相关，并且我们验证了circCAMSAP 1通过circCAMSAP 1/miR-145- 5 p/FLI 1途径发挥作用。
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. Osteosarcoma is the most common primary malignant bone tumor in adolescents. This study aims to explore the roles of circular RNA circCAMSAP1 in osteosarcoma and explore the underlying mechanisms. We showed that circCAMSAP1 is positively correlated with osteosarcoma tumorigenesis, and we validated that circCAMSAP1 functions through a circCAMSAP1/miR-145-5p/FLI1 pathway.
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影响因子：
9
作者：
Ji, Xianglu;Shan, Liping;He, Ming
通讯作者：
He, Ming
DOI：
10.1073/pnas.90.12.5752
发表时间：
1993-06-15
影响因子：
11.1
作者：
MAY, WA;GISHIZKY, ML;DENNY, CT
通讯作者：
DENNY, CT
影响因子：
--
作者：
Martin JW;Squire JA;Zielenska M
通讯作者：
Zielenska M
影响因子：
46.9
作者：
Jeck, William R.;Sharpless, Norman E.
通讯作者：
Sharpless, Norman E.
DOI：
10.2165/00148581-200810050-00005
发表时间：
2008-01-01
期刊：
Paediatric drugs
影响因子：
--
作者：
Chou, Alexander J;Geller, David S;Gorlick, Richard
通讯作者：
Gorlick, Richard