Elevated microRNA-126 is associated with high vascular endothelial growth factor receptor 2 expression levels and high microvessel density in colorectal cancer

Abstract

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 5.8 (95% CI,), 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.

The prognostic value of microRNA-126 and microvessel density in patients with stage II colon cancer: results from a population cohort

“…A similar positive relationship between these two parameters has been seen in previous studies of patients with CRC [31,33], while negative correlations have been detected in other solid tumours [19,20]. Possible reasons for these divergent results are; inclusion of multiple different tumour types, disease stages, comparability of samples (non-adjacent sections as in this study), analytic methodology, ethnicity, and technical differences between quantification of immunohistochemical estimates and the PCR outcome.…”

“…The study by Li et al demonstrated a similar significant relationship between high malignancy grade and low miRNA-126 expression [30], while two other studies did not identify any significant relationships [21,31]. This may be caused by rather small sample sizes (66 < N < 110) and most importantly heterogeneous samples including stage I through IV disease.…”

Syndecan-1 responsive microRNA-126 and 149 regulate cell proliferation in prostate cancer

“…On the other hand, increased expression of miR-126 is associated with neo-angiogenesis in colorectal cancer [29], and promotes metastasis in prostate cancer [30].…”

MiR-381 inhibits migration and invasion in human gastric carcinoma through downregulatedting SOX4

“…Despite of their short length, miRNAs have been confirmed to act vital important roles in various biological processes including glycometabolism (4), angiogenesis (5), cell growth (6) and movement (7).…”