Reduced expression of microRNA-497 is associated with greater angiogenesis and poor prognosis in human gliomas
Reduced expression of microRNA-497 is associated with greater angiogenesis and poor prognosis in human gliomas
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DOI：
10.1016/j.humpath.2016.04.022
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发表时间：
2016-12-01
期刊：
影响因子：
3.3
通讯作者：
Fan, Yimin
中科院分区：
文献类型：
--
作者：
Feng, Fuqiang;Kuai, Dong;Fan, Yimin
microRNA（miR）-497在几种恶性肿瘤中发挥肿瘤抑制作用，并参与胶质瘤侵袭性和对化疗的抗性。为了进一步了解miR-497在人脑胶质瘤中的临床意义，采用实时定量聚合酶链反应检测了110对新鲜制备的脑胶质瘤和非肿瘤脑组织中miR-497的表达。统计分析miR-497表达与胶质瘤患者临床病理特征及总生存期的关系。还进行了功能获得测定以检查miR-497在胶质瘤血管生成中的作用。miR-497在人脑胶质瘤组织中的表达显著低于非肿瘤脑组织（P <0.001）。此外，低miR-497表达与高世界卫生组织分级（P <0.001）和低Karnofsky表现评分（P = 0.02）显著相关。此外，低miR-497表达的胶质瘤患者的生存期明显短于高miR-497表达的患者（P = .001）。在胶质瘤细胞中强制表达miR-497抑制共培养的人脑微血管内皮细胞的管形成。我们还发现miR-497在胶质瘤细胞中的过表达导致血管内皮生长因子的表达降低。总之，miR-497可能是人类神经胶质瘤中有利的预后标志物，部分原因是作为血管生成的负调节因子，这意味着其作为这种癌症的治疗靶点的潜力。(C)2016 Elsevier Inc. All rights reserved.
MicroRNA (miR)-497 plays a tumor-suppressive role in several malignancies and is involved in glioma invasiveness and resistance to chemotherapy. To add to the knowledge of the clinical significance of miR-497 in human gliomas, quantitative real-time polymerase chain reaction was performed to detect the expression of miR-497 in 110 pairs of freshly prepared glioma and nonneoplastic brain tissues. Then the associations of miR-497 expression with various clinicopathological characteristics and overall survival of glioma patients were estimated statistically. Gain-of-function assays were also performed to examine the role of miR-497 in glioma angiogenesis. The expression of miR-497 in human glioma tissues was significantly lower than in nonneoplastic brain tissues (P < .001). In addition, low miR-497 expression was significantly associated with advanced World Health Organization grade (P < .001) and low Karnofsky performance scores (P = .02). Moreover, the survival of glioma patients with low miR-497 expression was dramatically shorter than that of patients with high miR-497 expression (P = .001). Forced expression of miR-497 in glioma cells inhibited tube formation by cocultured human brain microvascular endothelial cells. We also found that miR-497 overexpression in glioma cells led to decreased expression of vascular endothelial growth factor. In conclusion, miR-497 may be a favorable prognostic marker in human gliomas, in part by being a negative regulator of angiogenesis, implying its potential as a therapeutic target for this cancer. (C) 2016 Elsevier Inc. All rights reserved.