miR-632 promotes gastric cancer progression by accelerating angiogenesis in a TFF1-dependent manner
miR-632 promotes gastric cancer progression by accelerating angiogenesis in a TFF1-dependent manner
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DOI：
10.1186/s12885-018-5247-z
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发表时间：
2019-01-07
期刊：
影响因子：
3.8
通讯作者：
Ren, Jianlin
中科院分区：
文献类型：
--
作者：
Shi, Ying;Huang, Xiaoxiao;Ren, Jianlin
胃癌（Gastric cancer，GC）是世界范围内常见的恶性肿瘤。异常的miRNA表达有助于恶性细胞的行为，并且在临床前研究中，miRNA靶向已经显示出改善GC治疗的潜力。我们目前的研究表明，miR-632以三叶因子1（TFF 1）依赖性方式促进GC进展。方法我们收集GC组织和血清样本，使用实时PCR检测miR-632表达。使用双荧光素酶报告基因测定来鉴定miR-632是否直接调节TFF 1表达。在有或没有miR-632处理的情况下进行管形成和内皮细胞募集测定。结果胃癌组织和血清中miR-632高表达，与TFF 1呈负相关。miR-632通过负调节GC细胞中的TFF 1来改善管形成和内皮细胞募集。重组TFF 1逆转miR-632介导的血管生成。TFF 1是miR-632的靶基因之一。结论miR-632通过TFF 1依赖的方式促进胃癌血管生成，从而促进胃癌的进展。靶向miR-632可能是GC患者的潜在治疗方法。
BackgroundGastric cancer (GC) is a common malignant disease worldwide. Aberrant miRNAs expression contributes to malignant cells behaviour, and in preclinical research, miRNA targeting has shown potential for improving GC therapy. Our present study demonstrated that miR-632 promotes GC progression in a trefoil factor 1 (TFF1)-dependent manner.MethodsWe collected GC tissues and serum samples to detect miR-632 expression using real-time PCR. A dual-luciferase reporter assay was used to identify whether miR-632 directly regulates TFF1 expression. Tube formation and endothelial cell recruitment assays were performed with or without miR-632 treatment. Western blot and in situ hybridization assays were performed to detect angiogenesis and endothelial recruitment markers that are affected by miR-632.ResultsOur results showed that miR-632 is highly expressed in GC tissue and serum and negatively associated with TFF1 in GC. miR-632 improves tube formation and endothelial cell recruitment by negatively regulating TFF1 in GC cells. Recombinant TFF1 reversed miR-632-mediated angiogenesis. TFF1 is a target gene of miR-632.ConclusionsOur study demonstrated that miR-632 promotes GC progression by accelerating angiogenesis in a TFF1-dependent manner. Targeting of miR-632 may be a potential therapeutic approach for GC patients.