Circular RNA 0001785 regulates the pathogenesis of osteosarcoma as a ceRNA by sponging miR-1200 to upregulate HOXB2
Circular RNA 0001785 regulates the pathogenesis of osteosarcoma as a ceRNA by sponging miR-1200 to upregulate HOXB2
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DOI：
10.1080/15384101.2019.1618127
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发表时间：
2019-05-23
期刊：
影响因子：
4.3
通讯作者：
Zhang, Xiaojing
中科院分区：
文献类型：
--
作者：
Li, Shenglong;Pei, Yi;Zhang, Xiaojing
环状RNA(CircRNAs)是近年来出现的一种很有前途的肿瘤治疗靶点。骨肉瘤是儿童和青少年中最常见的原发骨肿瘤，也是第三位常见的癌症。本研究首先对骨肉瘤的CircRNA芯片进行了分析，选择了CIRC-0001785作为研究对象。本研究旨在全面探讨CIRC-0001785在骨肉瘤发生发展过程中的表达模式及其生物学功能。测定了正常人成骨细胞系和骨肉瘤细胞系中CIRC-0001785和miR-1200的相对表达水平。生物信息学分析预测了miR-1200与HOXB2和CIRC-0001785的结合关系，而双荧光素酶报告基因分析进一步验证了这种关系。用流式细胞仪和EDU法检测CIRC-0001785/miR-1200/HOXB_2轴对骨肉瘤细胞的调控作用。与基因芯片分析一致，CIRC-0001785在骨肉瘤细胞系中高表达。CIRC-0001785基因敲除可抑制骨肉瘤细胞的增殖能力，但可诱导骨肉瘤细胞发生凋亡。此外，我们还证实了circ-0001785与miR-1200竞争性结合，从而上调了其靶基因HOXB2。Western印迹分析表明，CIRC-0001785调控骨肉瘤中PI3K/Akt信号通路和Bcl2家族信号转导通路。综上所述，CIRC-0001785通过海绵MIR-1200上调HOXB2的表达来调控骨肉瘤的发病。
Circular RNAs (circRNAs) are recently emerged to be promising therapeutic targets of tumors. Osteosarcoma is the most prevalent primary bone tumor and the third most prevalent cancer in children and adolescents. This study firstly analyzed circRNA microarray of osteosarcoma and selected circ-0001785 as the study object. We aimed to comprehensively investigate the expression pattern and biological function of circ-0001785 in the progression of osteosarcoma. Relative levels of circ-0001785 and miR-1200 in the normal human osteoblast cell line and osteosarcoma cell lines were determined. Bioinformatics analyses predicted the binding relationship between miR-1200 to HOXB2 and circ-0001785, while dual-luciferase reporter gene assay further verified this relationship. Flow cytometry and EdU assay were used for evaluating the regulatory effects of circ-0001785/miR-1200/HOXB2 axis on osteosarcoma cells. Consistent with the microarray analysis, circ-0001785 was highly expressed in osteosarcoma cell lines. Knockdown of circ-0001785 attenuated proliferative ability, but induced the apoptosis of osteosarcoma cells. Furthermore, we confirmed that circ-0001785 competitively bound to miR-1200, thus up-regulating its target gene HOXB2. Western blot analyses revealed that circ-0001785 regulated the PI3K/Akt signaling and Bcl-2 family pathway in osteosarcoma. In conclusion, circ-0001785 regulates the pathogenesis of osteosarcoma by sponging miR-1200 to up-regulate HOXB2 expression.