CircHIPK3 sponges miR-558 to suppress heparanase expression in bladder cancer cells
CircHIPK3 sponges miR-558 to suppress heparanase expression in bladder cancer cells
复制标题
CircHIPK3 海绵 miR-558 抑制膀胱癌细胞中乙酰肝素酶的表达。
DOI：
10.15252/embr.201643581
复制
发表时间：
2017-09-01
期刊：
影响因子：
7.7
通讯作者：
Jiang, Guosong
中科院分区：
文献类型：
--
作者：
Li, Yawei;Zheng, Fuxin;Jiang, Guosong
越来越多的证据表明，环状RNA（circular RNA，circRNA）在基因表达调控中发挥着重要作用。在这项研究中，我们进行了RNA-seq，并从人类膀胱癌和正常膀胱组织中鉴定了6，154种不同的circRNA。我们发现，在人类膀胱癌组织中，数百种circRNA显著失调。我们进一步发现，circHIPK 3，也称为膀胱癌相关环状RNA-2（BCRC-2），在膀胱癌组织和细胞系中显著下调，并分别与膀胱癌分级、浸润以及淋巴结转移呈负相关。过表达circHIPK 3在体外有效抑制膀胱癌细胞的迁移、侵袭和血管生成，并在体内抑制膀胱癌的生长和转移。机制研究表明，circHIPK 3含有两个关键的结合位点的microRNA miR-558，并可以大量海绵miR-558抑制乙酰肝素酶（HPSE）的表达。综上所述，我们的研究结果提供了证据，证明circRNA作为“microRNA海绵”，并提出了一个新的治疗靶点，用于治疗膀胱癌。
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.