MicroRNA-140-5p inhibits cell proliferation and invasion by regulating VEGFA/MMP2 signaling in glioma

• Published in: Tumor biology 2017-04, Vol.39 (4), p.1010428317697558-1010428317697558
• Main Authors: Hu, Yuan, Li, Yanyan, Wu, Chun, Zhou, Liang, Han, Xiaoxiao, Wang, Qingyue, Xie, Xueshun, Zhou, Youxin, Du, Ziwei
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angiogenesis; Animals; Apoptosis; Apoptosis - genetics; Brain research; Cancer therapies; Cell cycle; Cell growth; Cell proliferation; Cell Proliferation - genetics; Central nervous system; Chemotherapy; Colorectal carcinoma; Disease resistance; Female; Gelatinase A; Gene expression; Gene Expression Regulation, Neoplastic; Glioma; Glioma - genetics; Glioma - pathology; Glioma cells; Hepatocellular carcinoma; Humans; Immunohistochemistry; Kinases; Male; Matrix metalloproteinase; Matrix Metalloproteinase 2 - genetics; Medical prognosis; Metalloproteinase; Metastasis; Mice; MicroRNAs - biosynthesis; MicroRNAs - genetics; Middle Aged; miRNA; Neoplasm Invasiveness - genetics; Non-coding RNA; Patients; Polymerase chain reaction; Protein expression; Proteins; Radiation therapy; Signal transduction; Signal Transduction - genetics; Surgery; Trauma; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Xenograft Model Antitumor Assays
• ISSN: 1010-4283; 1423-0380
• 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.