miR-1 inhibits the progression of colon cancer by regulating the expression of vascular endothelial growth factor

Abstract

MicroRNA (miR)-1 is associated with various human malignancies through repressing tumor growth, migration and angiogenesis. Recently, high-throughput transcriptional profiling confirmed that miR-1 is markedly downregulated in metastatic colorectal cancer; however, its biological functions and the specific underlying mechanisms in colorectal cancer (CRC) require further investigation. In this study, the expression of miR-1 in 111 CRC and paired normal tissue samples was measured using quantitative polymerase chain reaction analysis, and the association between miR-1 expression and clinical characteristics was evaluated. miR-1 was found to be significantly downregulated in CRC tissues compared with paired normal tissues, and in CRC cell lines compared with non-cancer cells (P<0.001), and was negatively associated with tumor size (P=0.001), differentiation (P=0.011), lymph node metastasis (P=0.001) and TNM stage (P=0.001). Further experiments revealed that miR-1 inhibited the migration and invasion of HCT116 and ClonA1 cells, and inhibited cell proliferation by affecting the cell cycle. Vascular endothelial growth factor (VEGF) was found to be a potential target of miR-1 by biological prediction, and further investigation confirmed that miR-1 significantly inhibited the expression and paracrine function of VEGF. In CRC tissues, the expression of VEGF was negatively correlated with miR-1. The low expression of miR-1 in CRC may be one of the reasons for the abnormally high expression of VEGF; the upregulation of miR-1 expression may inhibit cancer progression by downregulating VEGF. These findings indicate that treatment with miR-1 may be a novel method of tumor suppression, and provide a theoretical and experimental basis for the further targeted treatment of CRC through the regulation of miR-1 and VEGF expression.