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microRNA-1228(⁎) impairs the pro-angiogenic activity of gastric cancer cells by targeting macrophage migration inhibitory factor.

microRNA-1228(⁎) impairs the pro-angiogenic activity of gastric cancer cells by targeting macrophage migration inhibitory factor.
Author Information (click to view)

Jia L, Chen J, Xie C, Shao L, Xu Z, Zhang L,


Jia L, Chen J, Xie C, Shao L, Xu Z, Zhang L, (click to view)

Jia L, Chen J, Xie C, Shao L, Xu Z, Zhang L,

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Life sciences 2017 04 29180() 9-16 pii S0024-3205(17)30202-3
Abstract

Our previous study has shown that microRNA-1228(⁎) (miR-1228(⁎)) is downregulated in gastric cancer tissues and restoration of its expression retards tumor growth in a gastric cancer xenograft model. In this work, we aimed to explore the role of miR-1228(⁎) in gastric cancer cell cycle progression and angiogenesis and to identify its functional target gene(s). It was found that miR-1228(⁎) overexpression significantly inhibited the proliferation and colony formation of gastric cancer cells, compared to vector-transfected cells. As determined by propidium iodide staining, overexpression of miR-1228(⁎) resulted in an enrichment of G0/G1 phase cells in gastric cancer cells. miR-1228(⁎)-overexpressing cells showed a significant reduction of vascular endothelial growth factor expression and secretion. Conditioned media from miR-1228(⁎)-overexpressing cells showed a reduced capacity to promote endothelial cell migration and tube formation. Mechanistically, macrophage migration inhibitory factor (MIF) was identified as a direct target gene of miR-1228(⁎). Enforced expression of MIF rescued gastric cancer cells from miR-1228(⁎)-mediated suppression of proliferation and angiogenesis. In vivo xenograft mouse studies further demonstrated that co-expression of MIF with miR-1228(⁎) in gastric cancer cells significantly restored tumor growth and increased microvascular density. Taken together, miR-1228(⁎) acts as a negative regulator of gastric cancer growth and angiogenesis through downregulation of MIF. This work suggests miR-1228(⁎) as a potential target for anti-angiogenic therapy against gastric cancer.

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