Circ_0008532 promotes bladder cancer progression by regulation of the miR-155-5p/miR-330-5p/MTGR1 axis
Circ_0008532 promotes bladder cancer progression by regulation of the miR-155-5p/miR-330-5p/MTGR1 axis
复制标题
Circ_0008532通过调节miR-155-5p/miR-330-5p/MTGR1轴促进膀胱癌进展
DOI：
10.1186/s13046-020-01592-0
复制
发表时间：
2020-05-27
影响因子：
11.3
通讯作者：
Hou, Teng
中科院分区：
文献类型：
--
作者：
Chen, Liang;Yang, Xiong;Hou, Teng
方法采用实时荧光定量PCR和蛋白质印迹法检测膀胱癌细胞系和组织中Circ_0008532、MTGR 1和miR-155 - 5p/miR-330 - 5p的表达水平。进行体外和体内测定以研究circ_0008532在膀胱癌细胞中的肿瘤发生中的功能。使用生物信息学工具预测Circ_0008532、MTGR 1和miR-155 - 5p/miR-330 - 5p的关系，并通过RNA-FISH、RIP和荧光素酶测定进行验证。通过GSEA分析和western blotting检测circ_0008532对Notch信号通路的影响。结果我们发现circ_0008532在BC细胞系和组织中上调。此外，circ_0008532的过表达促进BC细胞的侵袭能力，而circ_0008532的沉默抑制BC细胞的侵袭能力。结论Circ_0008532可能通过一个新的circ_0008532/miR-155 - 5p，与miR-155 - 5p和miR-330 - 5p相互作用，介导miR-155 - 5p/miR-330 - 5p靶基因MTGR 1的表达和下游Notch信号转导。miR-330 - 5p/MTGR1/Notch通路轴，这反过来可能为膀胱癌的管理提供潜在的生物标志物和治疗靶点。
BackgroundCircular RNAs (circRNAs) have been associated with bladder cancer (BC), but the specific underlying molecular mechanism of their association with BC development has not been fully explored.MethodsLevels of Circ_0008532, MTGR1 and miR-155-5p/miR-330-5p in bladder cancer cell lines and tissues were determined with quantitative real-time PCR and western blotting assays. In vitro and in vivo assays were performed to investigate the function of circ_0008532 in tumorigenesis in bladder cancer cells. The relationships of Circ_0008532, MTGR1 and miR-155-5p/miR-330-5p were predicted using bioinformatic tools and verified by RNA-FISH, RIP and luciferase assays. The effects of circ_0008532 on the Notch signaling pathway were determined by GSEA analysis and western blotting assay.ResultsWe found that circ_0008532 is upregulated in BC cell lines and tissues. Moreover, overexpression of circ_0008532 promotes, and silencing of circ_0008532 inhibits the capacity for invasive in BC cells. In addition, circ_0008532 can directly interact with miR-155-5p and miR-330-5p as an miRNA sponge which mediates the expression of the miR-155-5p/miR-330-5p target gene MTGR1 and downstream Notch signaling.ConclusionsCirc_0008532 may act as an oncogene in BC through a novel circ_0008532/miR-155-5p, miR-330-5p /MTGR1/Notch pathway axis, which in turn may provide potential biomarkers and a therapeutic target for the management of bladder cancer.