miR-26a/b Inhibit Tumor Growth and Angiogenesis by Targeting the HGF-VEGF Axis in Gastric Carcinoma.
miR-26a/b Inhibit Tumor Growth and Angiogenesis by Targeting the HGF-VEGF Axis in Gastric Carcinoma.
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miR-26a/b 通过靶向胃癌中的 HGF-VEGF 轴抑制肿瘤生长和血管生成。
DOI：
10.1159/000479412
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Ba Yi
中科院分区：
文献类型：
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作者：
Si Yiran;Zhang Haiyang;Ning Tao;Bai Ming;Wang Yi;Yang Haiou;Wang Xinyi;Li Jialu;Ying Guoguang;Ba Yi
背景与目的肝细胞生长因子（HGF）在多种肿瘤中的异常表达与肿瘤的增殖、转移及血管生成密切相关。方法采用免疫组化方法检测HGF在胃癌组织中的表达特征，Western blot检测目的蛋白的表达水平。通过qRT-PCR检测miR-26 a/B和靶mRNA的相对水平。我们使用生物信息学工具来寻找可能靶向HGF的miRNAs。荧光素酶测定用于确认直接靶向。此外，通过体外细胞增殖和迁移实验以及体内小鼠移植瘤模型研究了miR-26 a/B和HGF的功能。结果胃癌组织中HGF蛋白表达明显增加，而miR-26 a/B表达明显下调。miR-26 a/B与HGF mRNA的3 '-UTR在特异性靶向位点直接结合。我们证明了通过miR-26 a/B过表达抑制HGF-VEGF途径抑制胃癌细胞增殖和迁移。结论miR-26 a/B可通过靶向HGF-VEGF轴抑制肿瘤的发生和血管生成，有望成为胃癌临床靶向治疗的一种新方法。
Background/AimsAbnormal expression of HGF is found in various cancers and correlates with tumor proliferation, metastasis and angiogenesis. However, the regulatory mechanism of the HGF-VEGF axis remains unclear.MethodsThe expression characteristic of HGF in human gastric cancer tissues was shown by an immunohistochemistry assay, and the expression levels of target protein were detected by Western blot. The relative levels of miR-26a/b and target mRNA were examined by qRT-PCR. We used bioinformatics tools to search for miRNAs that can potentially target HGF. A luciferase assay was used to confirm direct targeting. Furthermore, the functions of miR-26a/b and HGF were evaluated by cell proliferation and migration assays in vitro and by the mouse xenograft tumor model in vivo.ResultsWe found that the HGF protein was clearly increased while miR-26a/b were dramatically down-regulated in gastric cancer. miR-26a/b directly bind to the 3’-UTR of HGF mRNA at specific targeting sites. We demonstrated that the repression of the HGF-VEGF pathway by miR-26a/b overexpression suppressed gastric cancer cell proliferation and migration. Furthermore, miR-26a/b also showed an anti-tumor effect in the xenograft mouse model by suppressing tumor growth and angiogenesis.ConclusionsmiR-26a/b could suppress tumor tumorigenesis and angiogenesis by targeting the HGF-VEGF axis and could serve as a potential treatment modality for targeted therapy in the clinical treatment of gastric cancer.