CircHIPK3 sponges miR‐558 to suppress heparanase expression in bladder cancer cells. (9th August 2017)

• Record Type: Journal Article
• Authors: Li, Yawei; Zheng, Fuxin; Xiao, Xingyuan; Xie, Fei; Tao, Dan; Huang, Chao; Liu, Dong; Wang, Miao; Wang, Liang; Zeng, Fuqing; Jiang, Guosong
• Is Part Of: EMBO reports. Volume 18:Number 9(2017)
• Page Start: 1646
• Page End: 1659
• Publication Date: 2017-08-09
• Subjects: bladder cancer -- circHIPK3 -- circular RNA -- heparanase -- miR‐558; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201643581
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: Increasing evidences suggest that circular RNAs (circRNAs) exert crucial functions in regulating gene expression. In this study, we perform RNA‐seq and identify 6, 154 distinct circRNAs from human bladder cancer and normal bladder tissues. We find that hundreds of circRNAs are significantly dysregulated in human bladder cancer tissues. We further show that circHIPK3, also named bladder cancer‐related circular RNA‐2 (BCRC‐2), is significantly down‐regulated in bladder cancer tissues and cell lines, and negatively correlates with bladder cancer grade, invasion as well as lymph node metastasis, respectively. Over‐expression of circHIPK3 effectively inhibits migration, invasion, and angiogenesis of bladder cancer cells in vitro and suppresses bladder cancer growth and metastasis in vivo . Mechanistic studies reveal that circHIPK3 contains two critical binding sites for the microRNA miR‐558 and can abundantly sponge miR‐558 to suppress the expression of heparanase (HPSE). Taken together, our findings provide evidence that circRNAs act as "microRNA sponges", and suggest a new therapeutic target for the treatment of bladder cancer. Synopsis: Circular RNAs are suggested to exert crucial functions in regulating gene expression. Here, deregulated circRNAs in human bladder cancer tissues are identified, and circHIPK3 is shown to act as a tumour suppressive microRNA sponge. circHIPK3 is down‐regulated in human bladder cancer tissues and cell lines. circHIPK3 efficiently sponges miR‐558 in bladder cancer cells. circHIPK3 inhibits cancer aggressiveness and metastasis by targeting the miR‐558/heparanase axis. Abstract : Circular RNAs are suggested to exert crucial functions in regulating gene expression. Here, deregulated circRNAs in human bladder cancer tissues are identified, and circHIPK3 is shown to act as a tumour suppressive microRNA sponge.