Hsa_circ_0068307通过miR-147/c-Myc轴调控介导膀胱癌细胞干细胞样特性。
Hsa_circ_0068307 mediates bladder cancer stem cell-like properties via miR-147/c-Myc axis regulation.
作者信息
Chen Qi, Yin Qiuping, Mao Yemeng, Zhang Zheyu, Wu Siqi, Cheng Zhang, Chen Xinan, Xu Hanren, Jin Shengming, Jiang Haowen, Yang Chen
机构信息
1Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.
2Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China.
出版信息
Cancer Cell Int. 2020 May 6;20:151. doi: 10.1186/s12935-020-01235-6. eCollection 2020.
BACKGROUND
Circular RNAs (circRNAs) play an essential role in the regulation of gene expression. However, the underlying mechanisms remain unknown. This study aimed to evaluate the role of hsa_circ_0068307 in bladder cancer (BCa).
METHODS
Rt-qPCR was used to detect hsa_circ_0068307 expression in BCa cell lines. The CCK8, colony formation, and Transwell assays were used to evaluate the effect of hsa_circ_0068307 on BCa cell migration and proliferation. Bioinformatics and luciferase reporter experiments were used to study the regulatory mechanism. Nude mouse xenografts were generated to examine the effect of hsa_circ_0068307 on tumor growth.
RESULTS
The results showed that hsa_circ_0068307 was upregulated in BCa cell lines. Downregulation of hsa_circ_0068307 suppressed cell migration and proliferation in T24 and UMUC3 cells. Hsa_circ_0068307 silencing suppressed cancer stem cell differentiation by upregulating miR-147 expression. Upregulation of miR-147 suppressed c-Myc expression, which is involved in cancer stem cell differentiation. Luciferase reporter assays confirmed that hsa_circ_0068307 upregulated c-Myc expression by targeting miR-147. In vivo studies showed that hsa_circ_0068307 knockdown suppressed T24 tumor growth.
CONCLUSIONS
These data indicate that downregulation of hsa_circ_0068307 reversed the stem cell-like properties of human bladder cancer through the regulation of the miR-147/c-Myc axis.
背景
环状RNA（circRNAs）在基因表达调控中发挥着重要作用。然而，其潜在机制仍不清楚。本研究旨在评估hsa_circ_0068307在膀胱癌（BCa）中的作用。
方法
采用逆转录定量聚合酶链反应（Rt-qPCR）检测hsa_circ_0068307在BCa细胞系中的表达。采用细胞计数试剂盒-8（CCK8）、集落形成和Transwell实验评估hsa_circ_0068307对BCa细胞迁移和增殖的影响。利用生物信息学和荧光素酶报告基因实验研究其调控机制。构建裸鼠异种移植模型以检测hsa_circ_0068307对肿瘤生长的影响。
结果
结果显示，hsa_circ_0068307在BCa细胞系中表达上调。下调hsa_circ_0068307可抑制T24和UMUC3细胞的迁移和增殖。hsa_circ_0068307沉默通过上调miR-147表达抑制癌症干细胞分化。miR-147上调抑制参与癌症干细胞分化的c-Myc表达。荧光素酶报告基因实验证实hsa_circ_0068307通过靶向miR-147上调c-Myc表达。体内研究表明，敲低hsa_circ_0068307可抑制T24肿瘤生长。
结论
这些数据表明，下调hsa_circ_0068307通过调控miR-147/c-Myc轴逆转人膀胱癌的干细胞样特性。
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