Circular RNA circ-ZKSCAN1 inhibits bladder cancer progression through miR-1178-3p/p21 axis and acts as a prognostic factor of recurrence
Circular RNA circ-ZKSCAN1 inhibits bladder cancer progression through miR-1178-3p/p21 axis and acts as a prognostic factor of recurrence
复制标题
环状RNA circ-ZKSCAN1通过miR-1178-3p/p21轴抑制膀胱癌进展并作为复发的预后因素
DOI：
10.1186/s12943-019-1060-9
复制
发表时间：
2019-09-03
期刊：
影响因子：
37.3
通讯作者：
Lin, Tianxin
中科院分区：
文献类型：
--
作者：
Bi, Junming;Liu, Hongwei;Lin, Tianxin
背景
环状RNA（circRNA）代表已显示在癌症进展中具有显著调节作用的调节RNA的亚类。然而，circRNA在膀胱癌（BCa）中的生物学功能在很大程度上是未知的。
方法
建立细胞侵袭模型，qPCR检测细胞侵袭相关的circRNA。利用上述方法，筛选出circ-ZKSCAN 1进行进一步研究。通过qPCR进行Circ-ZKSCAN 1表达和存活分析。采用Kaplan-Meier法绘制生存曲线，采用log-rank检验评估显著性。检测细胞增殖、迁移和侵袭以研究circ-ZKSCAN 1的功能。评估裸鼠中的肿瘤发生以确定circ-ZKSCAN 1在膀胱癌中的作用。进行生物素偶联探针下拉测定、FISH和荧光素酶报告基因测定以确认circ-ZKSCAN 1与microRNA之间的关系。RNA-seq揭示了下游基因的不同分子变化。
结果
在这里，我们发现circ-ZKSCAN 1在BCa组织和细胞系中下调。Circ-ZKSCAN 1水平与生存率、肿瘤分级、病理T分期和肿瘤复发相关。过表达的circ-ZKSCAN 1在体内外抑制细胞增殖、迁移、侵袭和转移。从机制上讲，我们证明了circ-ZKSCAN 1通过海绵状miR-1178- 3 p上调p21表达，这抑制了膀胱癌的侵袭性生物学行为。
结论
这些结果揭示了Circ-ZKSCAN 1通过一个新的circ-ZKSCAN 1/miR-1178- 3 p/p21轴发挥抑癌作用，该轴在BCa细胞的增殖、迁移和侵袭能力中具有重要作用，为研究circRNA在BCa进展中的作用提供了新的视角。
Background
Circular RNAs (circRNAs) represent a subclass of regulatory RNAs that have been shown to have significant regulatory roles in cancer progression. However, the biological functions of circRNAs in bladder cancer (BCa) are largely unknown.
Methods
Cell invasion models were established, and invasion-related circRNAs were detected by qPCR. Using above method, circ-ZKSCAN1 was picked out for further study. Circ-ZKSCAN1 expression and survival analyses were performed through qPCR. The survival curves were generated by the Kaplan-Meier method, and the log-rank test was used to assess the significance. Cell proliferation, migration and invasion were examined to investigate the function of circ-ZKSCAN1. Tumorigenesis in nude mice was assessed to determine the effect of circ-ZKSCAN1 in bladder cancer. Biotin-coupled probe pull-down assays, FISH and luciferase reporter assays were conducted to confirm the relationship between circ-ZKSCAN1 and microRNA. RNA-seq revealed different molecular changes in downstream genes.
Results
Here, we found that circ-ZKSCAN1 was downregulated in BCa tissues and cell lines. Circ-ZKSCAN1 levels were associated with survival, tumor grade, pathological T stage and tumor recurrence. Overexpressed circ-ZKSCAN1 inhibits cell proliferation, migration, invasion and metastasis in vitro and in vivo. Mechanistically, we demonstrated that circ-ZKSCAN1 upregulated p21 expression by sponging miR-1178-3p, which suppressed the aggressive biological behaviors in bladder cancer.
Conclusions
These results reveal that Circ-ZKSCAN1 acts as a tumor suppressor via a novel circ-ZKSCAN1/miR-1178-3p/p21 axis, which have the important role in the proliferation, migration and invasion ablitities of BCa cells and provide a novel perspective on circRNAs in BCa progression.