Department of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China; Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):231-235. doi: 10.1016/j.bbrc.2018.11.013. Epub 2018 Nov 12.
Bladder cancer (BCa) belongs to a popular urological malignancy and leads to large numbers of deaths worldwide. Recently, emerging evidences indicate that long noncoding RNAs (lncRNAs) are closely related with BC occurrence and progression. However, the function of lncRNA MAGI2-AS3 remains poorly understood in BC. In this present study, we screened out a novel lncRNA MAGI2-AS3 whose expression was downregulated in BCa tissues. We showed that MAGI2-AS3 downregulation in BCa patients indicated a poor prognosis. Functionally, we showed that MAGI2-AS3 overexpression inhibits proliferation, migration and invasion of BCa cells. Moreover, ectopic expression of MAGI2-AS3 suppresses BCa growth in vivo. Bioinformatics analysis revealed that MAGI2-AS3 could serve as a competing endogenous RNA (ceRNA) for miR-15b-5p. In the meantime, miR-15b-5p directly targeted CCDC19, a tumor suppressor in BCa. Rescue assays demonstrated that knockdown of CCDC19 restored the proliferation, migration and invasion of BCa cells suppressed by MAGI2-AS3 overexpression. In conclusion, this study identified a novel mechanism that MAGI2-AS3/miR-15b-5p/CCDC19 signaling pathway regulates BCa progression.
膀胱癌(BCa)属于一种常见的泌尿系统恶性肿瘤,在全球范围内导致大量死亡。最近,新出现的证据表明,长非编码 RNA(lncRNA)与 BCa 的发生和发展密切相关。然而,lncRNA MAGI2-AS3 在 BCa 中的功能仍知之甚少。在本研究中,我们筛选出一种新型的 lncRNA MAGI2-AS3,其在 BCa 组织中的表达下调。我们表明,BCa 患者中 MAGI2-AS3 的下调预示着预后不良。功能上,我们表明 MAGI2-AS3 过表达抑制 BCa 细胞的增殖、迁移和侵袭。此外,MAGI2-AS3 的异位表达抑制了 BCa 在体内的生长。生物信息学分析显示,MAGI2-AS3 可以作为 miR-15b-5p 的竞争性内源 RNA(ceRNA)。同时,miR-15b-5p 直接靶向 CCDC19,CCDC19 是 BCa 中的一种肿瘤抑制因子。挽救实验表明,CCDC19 的敲低恢复了 MAGI2-AS3 过表达抑制的 BCa 细胞的增殖、迁移和侵袭。总之,本研究确定了 MAGI2-AS3/miR-15b-5p/CCDC19 信号通路调节 BCa 进展的新机制。