Inhibition of miR-194 suppresses the Wnt/β-catenin signalling pathway in gastric cancer
Inhibition of miR-194 suppresses the Wnt/β-catenin signalling pathway in gastric cancer
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抑制 miR-194 可抑制胃癌中的 Wnt/β-catenin 信号通路
DOI：
10.3892/or.2018.6773
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发表时间：
2018-12-01
期刊：
影响因子：
4.2
通讯作者：
Jin, Zhe
中科院分区：
文献类型：
--
作者：
Peng, Yin;Zhang, Xiaojing;Jin, Zhe
越来越多的证据表明，microRNAs（miRs）通过与靶基因结合并调节基因表达，在多种发育过程和肿瘤发生中发挥着关键作用。Wnt/β-连环蛋白信号的持续激活与人类恶性肿瘤正相关。此外，miR-194失调与胃癌（GC）有关;然而，miR-194对GC致癌作用的分子机制仍有待阐明。目前的研究表明，miR-194在GC组织中上调，而SUFU负调节剂在GC细胞系中下调。随后，抑制miR-194减弱β-连环蛋白的核积累，从而阻断Wnt/β-连环蛋白信号传导。此外，SUFU介导了miR-194抑制诱导的β-catenin胞质转位。此外，与Wnt/β-catenin信号通路相关的基因被揭示为在通过miR-194抑制Wnt信号通路后下调。最后，结果表明，细胞凋亡显着增加响应于miR-194抑制，强烈提示胃癌中的miR-194的致癌作用。总之，这些发现表明miR-194可能通过激活Wnt/β-catenin信号通路促进胃癌发生，使其成为GC的潜在治疗靶点。
A mounting body of evidence has revealed that microRNAs (miRs) serve pivotal roles in various developmental processes, and in tumourigenesis, by binding to target genes and subsequently regulating gene expression. Continued activation of the Wnt/-catenin signalling is positively associated with human malignancy. In addition, miR-194 dysregulation has been implicated in gastric cancer (GC); however, the molecular mechanisms underlying the effects of miR-194 on GC carcinogenesis remain to be elucidated. The present study demonstrated that miR-194 was upregulated in GC tissues and SUFU negative regulator of edgehog signaling (SUFU) was downregulated in GC cell lines. Subsequently, inhibition of miR-194 attenuated nuclear accumulation of -catenin, which consequently blocked Wnt/-catenin signalling. In addition, the cytoplasmic translocation of -catenin induced by miR-194 inhibition was mediated by SUFU. Furthermore, genes associated with the Wnt/-catenin signalling pathway were revealed to be downregulated following inhibition of the Wnt signalling pathway by miR-194 suppression. Finally, the results indicated that cell apoptosis was markedly increased in response to miR-194 inhibition, strongly suggesting the carcinogenic effects of miR-194 in GC. Taken together, these findings demonstrated that miR-194 may promote gastric carcinogenesis through activation of the Wnt/-catenin signalling pathway, making it a potential therapeutic target for GC.