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Inhibition of PTTG1 expression by microRNA suppresses proliferation and induces apoptosis of malignant glioma cells

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The present study aimed to investigate the role of pituitary tumor-transforming gene 1 (PTTG1) in the proliferation, invasion and apoptosis of human malignant glioma U251 cells. Firstly, 2 microRNAs (miRNAs) targeting PTTG1 messenger (m)RNA were ligated into a pcDNA6.2-GW/EmGFP-miR expression vector. The recombinant plasmids, miRNA1 and miRNA-2 (miR2), were transfected into U251 cells using the liposome method. PTTG1 mRNA and protein levels were evaluated using quantitative polymerase chain reaction and western blot analysis. The proliferation and invasion abilities of U251 cells were determined using methylthiazol tetrazolium and Matrigel assays. Flow cytometry analysis with Annexin V/propidium iodide double staining was used to determine the percentage of apoptotic cells. PTTG1 expression was effectively suppressed by miR2. U251 cell growth was inhibited between 10.7 and 34.7% in the miR2 group compared with the blank group. The Matrigel assay demonstrated that the percentage of infiltrating U251 cells was significantly lower in the miR2 group (12.3±1.0%) compared to the blank group (24.7±1.4%; P<0.001) and the negative control group (24.0±2.0%; P<0.05). A higher percentage of apoptotic U251 cells were observed in the miR2 group compared with the blank group (53.6 vs. 32.4%) using flow cytometry due to cycle arrests at the G2/M phase. The miR2transfected U251 cells were subcutaneously injected into nude mice, and these mice possessed a decreased tumor tissue growth rate and higher percentage of apoptotic cells compared with the blank and negative control groups. In conclusion, PTTG1 gene expression in human malignant glioma U251 cells was effectively suppressed by exogenous miR2. The downregulation of PTTG1 induced glioma cell apoptosis and cell cycle arrest at the G2/M phase, which inhibited cell proliferation, reverse invasion and infiltration of glioma cells.
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Document Type: Research Article

Affiliations: 1: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China 2: Comprehensive Surgical Laboratory, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China

Publication date: November 1, 2016

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  • Oncology Letters is a monthly, peer-reviewed journal, available in print and online, that focuses on all aspects of clinical oncology, as well as in vitro and in vivo experimental model systems relevant to the mechanisms of disease.

    The principal aim of Oncology Letters is to provide the prompt publication of original studies of high quality that pertain to clinical oncology, chemotherapy, oncogenes, carcinogenesis, metastasis, epidemiology and viral oncology in the form of original research, reviews and case reports.
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