Hu Yuan, Li Yanyan, Wu Chun, Zhou Liang, Han Xiaoxiao, Wang Qingyue, Xie Xueshun, Zhou Youxin, Du Ziwei
Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
Tumour Biol. 2017 Apr;39(4):1010428317697558. doi: 10.1177/1010428317697558.
Glioma is the most common primary malignant tumor of the central nervous system, which results in both a poor prognosis and outcome because of the aggressive progression of disease, growth and resistance to surgery, chemotherapy, and radiotherapy. MiR-140-5p is a small, non-coding single-stranded RNA molecule, which was previously studied in the settings of human tongue cancer, hepatocellular carcinoma, and colorectal cancer. However, detailed data that formally demonstrate the contribution of miR-140-5p to glioma development are missing. Similarly, relatively little is known about the relationship of miR-140-5p, vascular endothelial growth factor A, and matrix metalloproteinase-2 in glioma progression. In this study, we found that miR-140-5p expression was significantly decreased in glioma tissues and in the glioma cell-lines U87 and U251 as compared with non-cancerous brain tissues by quantitative real-time polymerase chain reaction. In addition, miR-140-5p inhibited glioma cell proliferation and invasion and promoted glioma cell apoptosis both in vivo and in vitro. Interestingly, while the expression levels of miR-140-5p were higher in glioma cells, the messenger RNA or protein expression levels of vascular endothelial growth factor A and matrix metalloproteinase-2 were lower in glioma cells as determined by quantitative real-time polymerase chain reaction, western blot assay, and immunohistochemistry. By contrast, downregulation in the expression levels of miR-140-5p augmented the messenger RNA and protein expression levels of both vascular endothelial growth factor A and matrix metalloproteinase-2. These findings suggested that miR-140-5p inhibited glioma proliferation and invasion by regulating the vascular endothelial growth factor A/matrix metalloproteinase-2 signaling pathway both in vitro and in vivo.
胶质瘤是中枢神经系统最常见的原发性恶性肿瘤，由于疾病的侵袭性进展、生长以及对手术、化疗和放疗的抵抗，其预后和结局都很差。MiR-140-5p是一种小的非编码单链RNA分子，此前已在人类舌癌、肝细胞癌和结直肠癌中进行过研究。然而，缺乏正式证明miR-140-5p对胶质瘤发展作用的详细数据。同样，关于miR-140-5p、血管内皮生长因子A和基质金属蛋白酶-2在胶质瘤进展中的关系，人们了解得也相对较少。在本研究中，我们通过定量实时聚合酶链反应发现，与非癌性脑组织相比，胶质瘤组织以及胶质瘤细胞系U87和U251中miR-140-5p的表达显著降低。此外，miR-140-5p在体内和体外均抑制胶质瘤细胞增殖和侵袭，并促进胶质瘤细胞凋亡。有趣的是，通过定量实时聚合酶链反应、蛋白质印迹分析和免疫组织化学测定发现，虽然胶质瘤细胞中miR-140-5p的表达水平较高，但血管内皮生长因子A和基质金属蛋白酶-2的信使RNA或蛋白质表达水平较低。相反，miR-140-5p表达水平的下调增加了血管内皮生长因子A和基质金属蛋白酶-2的信使RNA和蛋白质表达水平。这些发现表明，miR-140-5p在体外和体内均通过调节血管内皮生长因子A/基质金属蛋白酶-2信号通路抑制胶质瘤的增殖和侵袭。
