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
  • View Affiliations

  • Published online on: Tuesday, July 23, 2013
  • Pages: 1976-1984
  • DOI: 10.3892/or.2013.2633

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.
Journal Cover

October 2013
Volume 30 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

2012 Impact Factor: 2.191
Ranked #33/202 Oncology
(total number of cites)

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APA
Zhang, Y., Wang, X., Xu, B., Wang, B., Wang, Z., Liang, Y., Zhou, J., Hu, J., & Jiang, B. (2013). Epigenetic silencing of miR-126 contributes to tumor invasion and angiogenesis in colorectal cancer. Oncology Reports, 30(4), 1976-1984.
MLA
Zhang, Wang, Xu, Wang, Wang, Liang, Zhou, Hu, and Bo Jiang. "Epigenetic silencing of miR-126 contributes to tumor invasion and angiogenesis in colorectal cancer." Oncology Reports Oncology Reports 30.4 (2013): 1976-1984.
Chicago
Zhang, Wang, Xu, Wang, Wang, Liang, Zhou, Hu, and Bo Jiang. "Epigenetic silencing of miR-126 contributes to tumor invasion and angiogenesis in colorectal cancer." Oncology Reports Oncology Reports 30 no. 4 (2013): 1976-1984.