title: Elevated microRNA-126 is associated with high vascular endothelial growth factor receptor 2 expression levels and high microvessel density in colorectal cancer.
abstract: MicroRNAs (miRNAs) are involved in a number of biological processes, including tumour biology. Pre-clinical studies have shown that miRNA-126 regulates signalling downstream of vascular endothelial growth factor receptor 2 (VEGFR-2) and, consequently, angiogenesis. The aim of this study was to analyse the possible relationship between miRNA-126, VEGFR-2 and angiogenesis in tumour tissue from patients with colorectal cancer (CRC). Tumour tissue was obtained from 81 patients. The miRNA-126 and VEGFR-2 gene expression levels were analysed by PCR and the protein concentrations of VEGFR-2 were analysed by ELISA. Angiogenesis, visualised by the endothelial cell marker CD105 combined with caldesmon, was assessed by immunohistochemistry and the microvessel density (MVD) technique. In situ hybridisation was performed for miRNA-126. Tumours were classified as low or high miRNA-126-expressing using the median as the cut-off. The median gene expression levels of VEGFR-2 were significantly lower in the tumours expressing low levels of miRNA-126, 0.30 (95% CI, 0.24-0.36), compared to those expressing high levels of miRNA-126, 0.48 (95% CI, 0.28-0.60), p=0.02. A positive association was observed with VEGFR-2 protein concentrations, p=0.06. The median MVD was significantly lower in the tumours expressing low levels of miRNA-126, 5.8 (95% CI, 5.33-6.67), compared to those expressing high levels, 8.0 (95% CI, 6.33-9.00), p<0.01. miRNA-126 was detected in endothelial cells by in situ hybridisation analysis. These results suggest that high levels of miRNA-126 in CRC are associated with high VEGFR-2 mRNA and protein levels and a higher density of newly formed microvessels. However, further studies should be conducted to analyse the clinical value of miRNA-126 in CRC.
authors: Department of Oncology, Vejle Hospital, Vejle.
authors: Torben Frøstrup
authors: TF
authors: Hansen
authors: Claus Lindbjerg
authors: CL
authors: Andersen
authors: Boye Schnack
authors: BS
authors: Nielsen
authors: Karen-Lise Garm
authors: KL
authors: Spindler
authors: Flemming Brandt
authors: FB
authors: Sørensen
authors: Jan
authors: J
authors: Lindebjerg
authors: Ivan
authors: I
authors: Brandslund
authors: Anders
authors: A
authors: Jakobsen