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微小RNA-185升高与透明细胞肾细胞癌中高血管内皮生长因子受体2表达水平及高微血管密度相关。

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.

作者信息

Yuan Hai-Xia, Zhang Jian-Ping, Kong Wen-Tao, Liu Yu-Jun, Lin Zong-Ming, Wang Wen-Ping, Guo Jian-Ming

机构信息

Department of Ultrasound, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, 200032, Shanghai, People's Republic of China.

出版信息

Tumour Biol. 2014 Dec;35(12):12757-63. doi: 10.1007/s13277-014-2602-9. Epub 2014 Sep 14.

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.

摘要

微小RNA(miRNA)参与包括肿瘤生物学在内的多种生物学过程。先前的研究表明,miRNA-185可调节血管内皮生长因子受体2(VEGFR-2)下游的信号传导,进而调控血管生成。本研究旨在分析肾细胞癌(RCC)患者样本中miRNA-185、VEGFR-2与血管生成之间的潜在关系。从82例患者获取肿瘤组织。通过PCR分析miRNA-185和VEGFR-2基因表达水平,采用ELISA检测VEGFR-2蛋白浓度。采用免疫组织化学和微血管密度(MVD)技术评估血管生成情况,以内皮细胞标志物CD34结合钙调蛋白进行可视化分析。对miRNA-185进行原位杂交。以中位数为界值,将肿瘤分为低miRNA-185表达组或高miRNA-185表达组。与高miRNA-185表达组(0.47,95%CI,0.27 - 0.59)相比,低miRNA-185表达组肿瘤中VEGFR-2的中位数基因表达水平显著更低,为0.31(95%CI,0.25 - 0.37),p = 0.02。VEGFR-2蛋白水平呈正相关,p = 0.06。与高miRNA-185表达组(8.0,95%CI,6.33 - 9.00)相比,低miRNA-185表达组肿瘤的中位数MVD显著更低,为6.8(95%CI,6.33 - 7.67),p < 0.01。通过原位杂交检测在内皮细胞中检测到miRNA-185。结果表明,RCC中高表达的miRNA-185与高VEGFR-2 mRNA和蛋白水平以及更高的微血管密度相关。然而,应进一步开展研究以分析miRNA-185在RCC中的预后价值。

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