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miR-126通过靶向VEGF-A在抑制食管癌进展中的关键作用。

The crucial role of miR-126 on suppressing progression of esophageal cancer by targeting VEGF-A.

作者信息

Kong Ranran, Ma Yuefeng, Feng Jie, Li Shaomin, Zhang Wei, Jiang Jiantao, Zhang Jin, Qiao Zhe, Yang Xiaoping, Zhou Bin

机构信息

Department of Thoracic Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, 710004 Xi'an, Shaanxi China.

Department of Nephrology, The First Affiliated Hospital, Xi'an Jiaotong University, 710061 Xi'an, Shaanxi China.

出版信息

Cell Mol Biol Lett. 2016 Jul 28;21:3. doi: 10.1186/s11658-016-0004-2. eCollection 2016.

DOI:10.1186/s11658-016-0004-2
PMID:28536606
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5415818/
Abstract

BACKGROUND

miR-126 is a key regulator of oncogenic processes. It is functionally linked to cellular proliferation, survival and migration. Vascular endothelial growth factor A (VEGF-A), which is regarded as a tumorgenesis activator, could directly target miR-126 in several tumors. However, the mechanism in esophageal cancer remains unclear.

METHODS AND RESULTS

In this study, the expression of miR-126 and VEGF-A were assessed in esophageal cancer tissues and esophageal cancer cell lines. We found that miR-126 has significantly lower expression in esophageal cancer tissues and esophageal cancer cell lines than in healthy tissues, while the expression of VEGF-A is high. Luciferase reporter assays were performed to investigate the relationship between VEGF-A and miR-126. We confirmed that VEGF-A is a target for miR-126. Furthermore, the proliferation of esophageal cancer cells with miR-126 overexpression and miR-126 knockdown was monitored using the MTT assay. The results showed that miR-126 could inhibit esophageal cancer cell proliferation in vitro. The effect of miR-126 was also detected in BALB/c nude mice with transplanted esophageal cancer cells. In vivo study showed that tumor growth was significantly suppressed by miR-126 overexpression.

CONCLUSIONS

We believe that restoring miR-126 levels may be a promising therapeutic approach in cases of esophageal cancer.

摘要

背景

miR-126是致癌过程的关键调节因子。它在功能上与细胞增殖、存活和迁移相关。血管内皮生长因子A(VEGF-A)被视为肿瘤发生激活剂,在多种肿瘤中可直接靶向miR-126。然而,其在食管癌中的机制仍不清楚。

方法与结果

在本研究中,评估了miR-126和VEGF-A在食管癌组织及食管癌细胞系中的表达。我们发现,与健康组织相比,miR-126在食管癌组织及食管癌细胞系中的表达显著降低,而VEGF-A表达较高。进行荧光素酶报告基因检测以研究VEGF-A与miR-126之间的关系。我们证实VEGF-A是miR-126的靶点。此外,使用MTT法监测了miR-126过表达和miR-126敲低的食管癌细胞的增殖情况。结果表明,miR-126在体外可抑制食管癌细胞增殖。在移植了食管癌细胞的BALB/c裸鼠中也检测了miR-126的作用。体内研究表明,miR-126过表达可显著抑制肿瘤生长。

结论

我们认为,恢复miR-126水平可能是食管癌治疗的一种有前景的方法。

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