Author:
Mei Bin,Chen Jiajie,Yang Ni,Peng Yang
Abstract
AbstractVascular endothelial growth factor receptor (VEGFR) and neuropilins (NRPs), a co-receptor of VEGF, play a key role in the formation and development of blood vessels and in tumour growth and metastasis. However, whether VEGFR1/2 and NRP1 are regulated by the same upstream mechanism is unclear, especially in gastric cancer. We used prediction tools to detect miRNAs that may simultaneously regulate VEGFR1/2 and NRP1, and we finally determined that miR-590 can simultaneously regulate VEGFR1/2 and NRP1 in gastric cancer. We discovered that miR-590 was downregulated in gastric cancer tissues and cell lines, and this was related to the dysregulation of the transcription factor SNAIL. In addition, the overexpression of miR-590 inhibits the migration, invasion, proliferation and D-MVA levels of gastric cancer cells in vivo and in vitro by targeting VEGFR1/2 and NRP1. We also demonstrated that miR-590 may be a useful marker for the prognosis of gastric cancer with Kaplan–Meier survival analysis. Since the epithelial-to-mesenchymal transition (EMT) is an important mechanism of tumour invasion and metastasis and VEGFR1/2 and NRP1 can promote the occurrence of EMT, we speculated that miR-590 can regulate the occurrence of EMT. Immunoblot and immunofluorescence analyses confirmed that the overexpression of miR-590 can inhibit the EMT in gastric cancer cells. Since SNAIL is also a mesenchymal marker, our results revealed a new, positive feedback loop. As a transcription factor, SNAIL inhibits the expression of miR-590, thereby upregulating the expression levels of NRP1 and VEGFR1/2; this leads to the development of EMT in gastric cancer and the upregulation of SNAIL.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology
Cited by
28 articles.
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