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.

miRNA Clusters with Down-Regulated Expression in Human Colorectal Cancer and Their Regulation

“…miR-1-3p expression shows negative correlation with tumour size, degree of differentiation, lymph node metastasis and tumour/nodus/metastasis stage (TNM) [ 85 , 86 , 87 ]. In vitro, miR-1-3p suppresses cell growth, migration, motility and glycolysis by targeting VEGF [ 87 ] and notch receptor 3 ( NOTCH3 ), which is known to be crucially involved in developmental processes by controlling cell fate decisions [ 88 ] as well as hypoxia-inducible factor 1 subunit alpha ( HIF1A ) [ 89 ]. The target genes of miR-1-3p also encode for NLR family apoptosis inhibitory protein ( NAIP ), which plays a role in the inhibition of apoptosis [ 86 ], and the focal adhesion protein LIM and SH3 protein 1 ( LASP1 ) [ 85 ].…”

MiR-1-3p Suppresses Colorectal Cancer Cell Proliferation and Metastasis by Inhibiting YWHAZ-Mediated Epithelial–Mesenchymal Transition

“…MicroRNAs (miRNAs) are a class of small non-coding RNA molecules of 20-22 nucleotides, which can directly bind to the 3′-untranslated region (3′-UTR) of target gene mRNAs to inhibit their translation (3). Increasing studies have reported that patients with tumor exist in a variety of disorders and abnormal expression of miRNAs.…”

Small RNA Sequencing Reveals Regulatory Roles of MicroRNAs in the Development of Meloidogyne incognita

“…In infectious rat lung work involving the nematode Angiostrongylus cantonensis , a pathogenic species causing eosinophilic meningitis in humans, the miR-1 expression level significantly increases during the infectious stage from larvae to young adults, and is the highest expressed miRNA in A. cantonensis during its parasitic cycle. Furthermore, the miR-1 is dysregulated in various cancers as a tumor-suppressive miRNA that targets multiple genes [25,26]. Overexpression of miR-1 is associated with increased chemosensitivity to anticancer drugs [27], and the downregulation of miR-1 is associated with the exposure to carcinogenic agents [28].…”