Elevated microRNA-185 is associated with high vascular endothelial growth factor receptor 2 expression levels and high microvessel density in clear cell renal cell carcinoma.

Abstract

MicroRNAs (miRNAs) are involved in a number of biological processes, including tumor biology. Previous studies have demonstrated that miRNA-185 regulates signaling downstream of vascular endothelial growth factor receptor 2 (VEGFR-2) and, consequently, angiogenesis. The aim of this study was to analyze the potential relationship between miRNA-185, VEGFR-2, and angiogenesis in samples from renal cell carcinoma (RCC) patients. Tumor tissue was obtained from 82 patients. The miRNA-185 and VEGFR-2 gene expression levels were analyzed by PCR, and the protein concentrations of VEGFR-2 were detected by ELISA. Angiogenesis, visualized by the endothelial cell marker CD34 combined with caldesmon, was assessed by immunohistochemistry and the microvessel density (MVD) technique. In situ hybridization was performed for miRNA-185. Tumors were classified as low or high miRNA-185-expressing using the median as the cutoff. The median gene expression levels of VEGFR-2 were significantly lower in the tumors expressing low levels of miRNA-185, 0.31 (95% CI, 0.25-0.37), compared to those expressing high levels of miRNA-185, 0.47 (95% CI, 0.27-0.59), p = 0.02. A positive association was certified with VEGFR-2 protein levels, p = 0.06. The median MVD was significantly lower in the tumors expressing low levels of miRNA-185, 6.8 (95% CI, 6.33-7.67), compared to those expressing high levels, 8.0 (95% CI, 6.33-9.00), p < 0.01. miRNA-185 was detected in endothelial cells by in situ hybridization detection. The results suggest that high levels of miRNA-185 in RCC are associated with high VEGFR-2 mRNA and protein levels and a higher density of microvessels. However, further investigation should be performed to analyze the prognostic value of miRNA-185 in RCC.