Circular RNA ACVR2A suppresses bladder cancer cells proliferation and metastasis through miR-626/EYA4 axis

Molecular Cancer

Ruihui Xie¹  Hongwei Liu¹  Tianxin Lin¹  Wei Dong¹  Qiong Wang¹  Qianghua Zhou¹  Meihua Yang¹  Yinjie Su¹  Dong Yan¹  Qingqing He¹  Junming Bi¹  Jian Huang¹ 

[1]0000 0004 1791 7851, grid.412536.7, Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107th Yanjiangxi Road, Guangzhou, China

[2]0000 0004 1791 7851, grid.412536.7, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107th Yanjiangxi Road, Guangzhou, China

关键词: circACVR2A;    miRNA-626;    EYA4;    Proliferation;    Metastasis;    Bladder cancer;   

DOI  :  10.1186/s12943-019-1025-z

来源: publisher

【 摘 要 】

BackgroundCircular RNAs (circRNAs) have been considered to mediate occurrence and development of human cancers, generally acting as microRNA (miRNA) sponges to regulate downstream genes expression. However, the aberrant expression profile and dysfunction of circRNAs in human bladder cancer remain to be investigated. The present study aims to elucidate the potential role and molecular mechanism of circACVR2A in regulating the proliferation and metastasis of bladder cancer.MethodscircACVR2A (hsa_circ_0001073) was identified by RNA-sequencing and validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. The role of circACVR2A in bladder cancer was assessed both in vitro and in vivo. Biotin-coupled probe pull down assay, biotin-coupled microRNA capture, dual-luciferase reporter assay, and fluorescence in situ hybridization were conducted to evaluate the interaction between circACVR2A and microRNAs.ResultsThe expression of circACVR2A was lower in bladder cancer tissues and cell lines. The down-regulation of circACVR2A was positively correlated with aggressive clinicopathological characteristics, and circACVR2A served as an independent risk factor for overall survival in bladder cancer patients after cystectomy. Our in vivo and in vitro data indicated that circACVR2A suppressed the proliferation, migration and invasion of bladder cancer cells. Mechanistically, we found that circACVR2A could directly interact with miR-626 and act as a miRNA sponge to regulate EYA4 expression.ConclusionscircACVR2A functions as a tumor suppressor to inhibit bladder cancer cell proliferation and metastasis through miR-626/EYA4 axis, suggesting that circACVR2A is a potential prognostic biomarker and therapeutic target for bladder cancer.

【 授权许可】

CC BY