Epigenetic silencing of miR-126 contributes to tumor invasion and angiogenesis in colorectal cancer

Zhang,Yu; Wang,Xinying; Xu,Binghong; Wang,Baocai; Wang,Zhongqiu; Liang,Yan; Zhou,Jieqiong; Hu,Jingjing; Jiang,Bo

doi:10.3892/or.2013.2633

Epigenetic silencing of miR-126 contributes to tumor invasion and angiogenesis in colorectal cancer

Authors:
- Yu Zhang
- Xinying Wang
- Binghong Xu
- Baocai Wang
- Zhongqiu Wang
- Yan Liang
- Jieqiong Zhou
- Jingjing Hu
- Bo Jiang
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Affiliations: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nangfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: July 23, 2013 https://doi.org/10.3892/or.2013.2633
Pages: 1976-1984

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Abstract

microRNAs (miRNAs) have been reported to play a crucial role in regulating a variety of genes pivotal for tumor metastasis. miR-126 is well known as one of the angiogenesis regulatory miRNAs. Recent studies have reported controversial roles of miR-126 in tumor progression. In this study, we sought to investigate the potential roles of miR-126 in colorectal cancer (CRC). By real-time PCR, miR-126 was shown to be downregulated in primary CRC tissues and cell lines. Restoration of miR-126 in CRC cells inhibited cell growth, migration and invasion. Using both in silico prediction and immunoblotting, we found that vascular endothelial growth factor (VEGF) was a target of miR-126. The interaction of miR-126 on the 3'UTR of VEGF mRNA was validated by luciferase reporter assay. Mechanistically, we found that the silencing of miR-126 was induced by promoter methylation of its host gene, EGFL7. Treatment with 5-aza-CdR restored miR-126 expression and thereby led to a decline in VEGF expression. Functionally, due to suppression of VEGF, enhanced miR-126 expression inhibited tumor neovasculature triggered by CRC cells. In conclusion, our findings suggest that DNA methylation-induced silencing of miR-126 contributes, at least in part, to tumor invasion and angiogenesis in CRC, through upregulation of VEGF expression. miR-126 may be a potential target for the therapeutic strategy against CRC.

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