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LSINCT5 通过与 NCYM 相互作用激活 Wnt/β-catenin 信号通路,促进膀胱癌的进展。

LSINCT5 activates Wnt/β-catenin signaling by interacting with NCYM to promote bladder cancer progression.

机构信息

Department of Andrology and Energy Medicine, Henan Provincial People's Hospital, Zhengzhou, 450003, China.

Department of Urology, Liaocheng People's Hospital, Liaocheng, 252000, China.

出版信息

Biochem Biophys Res Commun. 2018 Jul 20;502(3):299-306. doi: 10.1016/j.bbrc.2018.05.076. Epub 2018 May 30.

Abstract

Accumulating evidence has indicated that long non-coding RNAs (lncRNAs) are critically involved in tumor progression. In current study, we reported a novel lncRNA signature correlated with bladder cancer development. Particularly, the lncRNA long stress-induced noncoding transcript 5 (LSINCT5) is significantly upregulated in human bladder cancer cell lines and tumor specimens. Meanwhile, high LSINCT5 expression correlates with poor prognosis, enhances tumor sphere formation and invasion in vitro. In vivo xenograft tumor growth is also elevated by LSINCT5 overexpression. Mechanistic investigations showed that LSINCT5 could physically interact with NCYM, a de novo gene product from the MYCN cis-antisense RNA and inhibit GSK3β activity leading to enhanced Wnt/β-catenin signaling activation and epithelial mesenchymal transition (EMT). Taken together, our findings have created a novel LSINCT5 mediated process which facilitates bladder cancer progression and may provide a potential target for therapeutic intervention.

摘要

越来越多的证据表明,长非编码 RNA(lncRNA)在肿瘤进展中起着至关重要的作用。在本研究中,我们报道了一个与膀胱癌发生相关的新型 lncRNA 特征。特别是,lncRNA 长应激诱导非编码转录本 5(LSINCT5)在人膀胱癌细胞系和肿瘤标本中显著上调。同时,高 LSINCT5 表达与预后不良相关,增强了体外肿瘤球形成和侵袭能力。LSINCT5 的过表达也会增加体内异种移植肿瘤的生长。机制研究表明,LSINCT5 可以与 NCYM 相互作用,NCYM 是 MYCN 顺式反义 RNA 的从头基因产物,并抑制 GSK3β 活性,从而增强 Wnt/β-catenin 信号激活和上皮间质转化(EMT)。综上所述,我们的研究结果揭示了一个新的由 LSINCT5 介导的促进膀胱癌进展的过程,可能为治疗干预提供一个潜在的靶点。

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