The regulatory network of miR-141 in the inhibition of angiogenesis
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The miR-200 family, consisting of miR-200a/b/c, miR-141, and miR-429, is well known to inhibit epithelial-to-mesenchymal transition (EMT) in cancer invasion and metastasis. Among the miR-200 family members, miR-200a/b/c and miR-429 have been reported to inhibit angiogenesis. However, the role of miR-141 in angiogenesis remains elusive, as contradicting results have been found in different cancer types and tumor models. Particularly, the effect of miR-141 in vascular endothelial cells has not been defined. In this study, we used several in vitro and in vivo models to demonstrate that miR-141 in endothelial cells inhibits angiogenesis. Additional mechanistic studies showed that miR-141 suppresses angiogenesis through multiple targets, including NRP1, GAB1, CXCL12β, TGFβ2, and GATA6, and bioinformatics analysis indicated that miR-141 and its targets comprise a powerful and precise regulatory network to modulate angiogenesis. Taken together, these data not only demonstrate an anti-angiogenic effect of miR-141, further strengthening the critical role of miR-200 family in the process of angiogenesis, but also provides a valuable cancer therapeutic target to control both angiogenesis and EMT, two essential steps in tumor growth and metastasis.
KeywordsmiR-141 miR-200 family Angiogenesis Regulatory network
We appreciate Dr. Kerin Higa (City of Hope) and Dr. Wen Jin (Sigilon therapeutics) for critically reading the manuscript and for helpful discussions. This work was supported by the grants from the National Natural Science Foundation of China [Grant Numbers 31570786, 31600630 and 31770867] and the China Postdoctoral Science Foundation China [Grant Number 2016M591990].
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