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首页> 外文期刊>Cellular Physiology and Biochemistry >MiR-143-5p Deficiency Triggers EMT and Metastasis by Targeting HIF-1?± in Gallbladder Cancer
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MiR-143-5p Deficiency Triggers EMT and Metastasis by Targeting HIF-1?± in Gallbladder Cancer

机译:MiR-143-5p缺乏通过靶向HIF-1?±触发胆囊癌EMT和转移

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>Background/Aims: Early metastasis plays a pivotal role in tumor-caused death in gallbladder cancer (GBC) patients. Increasing evidence suggest that miR-143-5p is an active player involved in cancer metastasis and a potential therapeutic target. However, its role in the development of GBC cells remains unclear. The aim of this study is to reveal the inhibiting effects of miR-143-5p on the proliferation and metastasis in GBC. Methods: Quantitative real-time PCR were used to investigate miR-143-5p and its target HIF-1?± mRNA levels. Protein expression was measured by immunohistochemistry and western blot. The function and regulation mechanism of miR-143-5p was confirmed by MTS, colony formation, wound healing, transwell, and luciferase reporter assays. Results: miR-143-5p was first found significantly reduced in GBC tissues compared with corresponding noncancerous gallbladder tissues. In addition, miR-143-5p deficiency correlated well with larger tumor size, advanced TNM stage, and poorer survival rate. In vitro, miR-143-5p addition dramatically suppressed GBC cells proliferation, migration and invasion, whereas miR-143-5p antisense led the opposite effects. Further elucidating the molecular mechanism inside, we found miR-143-5p exerted its inhibitory function through downregulating the expression of HIF-1?±, which further reduced Twist1 and impeded epithelial-mesenchymal transition (EMT). Conclusions: Altogether, our studies identified a novel regulator, miR-143-5p, implicated in GBC prognosis through targeting HIF-1?±/EMT related signaling pathway, which could serve as a biomarker and therapeutic target for GBC.
机译:> 背景/目标: 早期转移在胆囊癌(GBC)患者的肿瘤致死中起着关键作用。越来越多的证据表明,miR-143-5p是参与癌症转移的活跃分子,并且是潜在的治疗靶标。但是,其在GBC细胞发育中的作用仍不清楚。这项研究的目的是揭示miR-143-5p对GBC增殖和转移的抑制作用。 方法: 使用实时定量PCR研究miR-143-5p及其目标HIF-1α±mRNA水平。通过免疫组织化学和蛋白质印迹测量蛋白质表达。通过MTS,集落形成,伤口愈合,transwell和荧光素酶报告基因检测证实了miR-143-5p的功能和调节机制。 结果: 首先发现,与相应的非癌性胆囊组织相比,GBC组织中的miR-143-5p明显减少。此外,miR-143-5p缺乏与较大的肿瘤大小,晚期TNM分期和较差的生存率密切相关。 在体外,miR-143-5p的添加显着抑制了GBC细胞的增殖,迁移和侵袭,而miR-143-5p的反义导致了相反的作用。进一步阐明内部的分子机制,我们发现miR-143-5p通过下调HIF-1α±的表达发挥其抑制功能,从而进一步降低Twist1并阻止上皮-间质转化(EMT)。 结论: 总之,我们的研究确定了一种新型的调控因子miR-143-5p,其通过靶向HIF-1?/ EMT相关信号通路参与GBC预后。用作GBC的生物标志物和治疗靶标。

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