Int J Med Sci 2014; 11(1):17-23. doi:10.7150/ijms.7329 This issue

Research Paper

Hypoxia-Induced Deregulation of miR-126 and Its Regulative Effect on VEGF and MMP-9 Expression

Panpan Ye1,2, Jian Liu1,2, Fengying He1,2, Wen Xu1,2, Ke Yao1,2 ✉

1. Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University;
2. Zhejiang Provincial Key Lab of Ophthalmology, China.

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Ye P, Liu J, He F, Xu W, Yao K. Hypoxia-Induced Deregulation of miR-126 and Its Regulative Effect on VEGF and MMP-9 Expression. Int J Med Sci 2014; 11(1):17-23. doi:10.7150/ijms.7329. Available from

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Objective: miR-126, the miRNA considered to be specially expressed in endothelial cells and hematopoietic progenitor cells, is strongly associated with angiogenesis. The purpose is to evaluate the role of miR-126 in hypoxia-induced angiogenesis and the possible mechanisms. Methods: The expression of miR-126 was detected in hypoxia-treated RF/6A cells and diabetic retinas using real-time PCR. The miR-126 was up- or down-regulated by transfecting miR-126-mimics or inhibitors into RF/6A cells. Cell cycle analysis was performed using flow cytometry. The protein levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were assessed by immunoblotting. Results: A significantly decreased expression of miR-126 was found in hypoxia-treated RF/6A cells in a time-dependent manner compared with normoxic condition. The expression of miR-126 was also reduced in the retina tissue of streptozotocin-induced diabetic rats. The expression of VEGF and MMP-9 proteins was increased in hypoxia-induced RF/6A cells. In the functional analysis, miR-126-mimic significantly reduced the percentage of RF/6A cells in S phases compared with the negative control under hypoxic conditions. Furthermore, the VEGF and MMP-9 protein levels were sharply decreased in hypoxia-induced RF/6A cells pretreated with miR-126-mimics and increased in the cells pretreated with miR-126-inhibitors. Conclusions: miR-126 is down-regulated under hypoxic condition both in vitro and in vivo and may halt the hypoxia-induce neovascularization by suspending the cell cycle progression and inhibiting the expression of VEGF and MMP-9.

Keywords: MicroRNA-126, Hypoxia, Vascular endothelial growth factor, Matrix metalloproteinase-9, Diabetic retinopathy.