文章：

circINTS4/miR-146b/CARMA3轴促进膀胱癌的肿瘤发生

The circINTS4/miR-146b/CARMA3 axis promotes tumorigenesis in bladder cancer 

原文发布日期：2019-02-06 

英文摘要：

Accumulating evidence shows that circular RNAs (circRNAs) function as microRNA sponges that regulate gene expression in the progression of human cancers. However, the roles of circRNAs and functional miRNA sponges in bladder cancer (BC) remain largely unknown. In the present study, we applied bioinformatics methods and hypothesised that miR-146b may target the 3′-untranslated region (UTR) of CARMA3 mRNA and circINTS4 may serve as a sponge for miR-146b in BC tumorigenesis. Expression of circINTS4 was significantly increased in miR-146b-downregulated BC tissues and cell lines compared to adjacent normal tissues. Furthermore, circINTS4 was found to control multiple pathological processes, including cell proliferation and migration, the cell cycle and apoptosis. Regarding the mechanism, circINTS4 directly bound to miR-146b to inhibit its activity of targeting the 3′-UTR of CARMA3 mRNA. In addition, circINTS4 could activate the NF-kB signalling pathway and suppress the P38 MAPK signalling pathway in a CARMA3-mediated manner in BC cells. In summary, the circINTS4/miR-146b/CARMA3 axis might serve as a promising therapeutic target for BC intervention. 

摘要翻译： 

越来越多的证据表明，环状RNA（circRNA）通过作为microRNA海绵调控人类癌症发展进程中的基因表达。然而，环状RNA及其功能性miRNA海绵在膀胱癌（BC）中的作用机制尚不明确。本研究采用生物信息学方法提出假说：miR-146b可能靶向CARMA3 mRNA的3'-非翻译区（UTR），而circINTS4在膀胱癌肿瘤发生过程中可能作为miR-146b的海绵分子。与癌旁正常组织相比，在miR-146b低表达的膀胱癌组织和细胞系中，circINTS4的表达显著升高。进一步研究发现，circINTS4可调控多个病理过程，包括细胞增殖、迁移、细胞周期和凋亡。机制研究表明，circINTS4直接结合miR-146b，抑制其靶向CARMA3 mRNA 3'-UTR的活性。此外，在膀胱癌细胞中，circINTS4能以CARMA3介导的方式激活NF-kB信号通路并抑制P38 MAPK信号通路。综上所述，circINTS4/miR-146b/CARMA3轴可能成为膀胱癌干预治疗的潜在靶点。

原文链接：

The circINTS4/miR-146b/CARMA3 axis promotes tumorigenesis in bladder cancer