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首页> 外文期刊>Cell death & disease. >miR-491-5p, mediated by Foxi1, functions as a tumor suppressor by targeting Wnt3a/β-catenin signaling in the development of gastric cancer
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miR-491-5p, mediated by Foxi1, functions as a tumor suppressor by targeting Wnt3a/β-catenin signaling in the development of gastric cancer

机译：Foxi1介导的miR-491-5p通过靶向Wnt3a / β -catenin信号传导而在胃癌的发展中起到抑癌作用

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Accumulated evidence has suggested that microRNAs (miRNAs) have an important role in tumor development and progression by regulating diverse signaling pathways. However, the precise role of miRNAs in gastric cancer (GC) has not been elucidated. In this study, we describe the function and regulation network of miR-491-5p in GC. miR-491-5p is frequently downregulated in GC tissues compared with adjacent non-cancerous tissues. Forced expression of miR-491-5p significantly inhibits proliferation and colony formation, and promotes apoptosis in GC cells. Through bioinformatic analysis and luciferase assays, we confirm that miR-491-5p targets Wnt3a. Silencing Wnt3a inhibits cell proliferation and induces apoptosis. Similarly, restoration of Wnt3a counteracts the effects of miR-491-5p expression. Moreover, bioinformatic and luciferase assays indicate that the expression of miR-491-5p is regulated by Foxi1, which binds to its promoter and activates miR-491-5p expression. In conclusion, to the best of our knowledge, our findings are the first to demonstrate that Foxi1 is a key player in the transcriptional control of miR-491-5p and that miR-491-5p acts as an anti-oncogene by targeting Wnt3a/ β -catenin signaling in GC. Our study reveals that Foxi1/miR-491-5p/Wnt3a/ β -catenin signaling is critical in the progression of GC. Targeting the pathway described in this study may open up new prospects to restrict the progression of GC.
机译：积累的证据表明，microRNA（miRNA）通过调节多种信号通路在肿瘤的发生和发展中具有重要作用。但是，尚未阐明miRNA在胃癌（GC）中的确切作用。在这项研究中，我们描述了miR-491-5p在GC中的功能和调控网络。与相邻的非癌性组织相比，miR-491-5p在GC组织中经常被下调。 miR-491-5p的强制表达显着抑制增殖和集落形成，并促进GC细胞凋亡。通过生物信息学分析和荧光素酶测定，我们确认miR-491-5p靶向Wnt3a。沉默Wnt3a抑制细胞增殖并诱导凋亡。同样，Wnt3a的恢复抵消了miR-491-5p表达的影响。此外，生物信息学和荧光素酶测定表明，miR-491-5p的表达受Foxi1调控，Foxi1与其启动子结合并激活miR-491-5p的表达。总之，据我们所知，我们的发现是第一个证明Foxi1是miR-491-5p转录控制中的关键角色，而miR-491-5p通过靶向Wnt3a /充当抗癌基因。 GC中的β-连环蛋白信号传导。我们的研究表明，Foxi1 / miR-491-5p / Wnt3a /β-catenin信号传导在GC进展中至关重要。针对本研究中描述的途径可能会为限制GC的发展开辟新的前景。

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