Knockdown of PEBP4 inhibits human glioma cell growth and invasive potential via ERK1/2 signaling pathway
| Autor: | Song‐qing Wang, Qing‐bao Zhu, Shan‐cheng Guo, Yuan‐cheng Fang, Ren-qiang Huang, Yicheng Lu, Rui Chen, Feng Chen, Dong-liang Shi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Cancer Research Mice Nude Apoptosis Phosphatidylethanolamine Binding Protein Biology 03 medical and health sciences Mice 0302 clinical medicine Glioma medicine Biomarkers Tumor Tumor Cells Cultured Gene silencing Animals Humans Neoplasm Invasiveness Molecular Biology Cell Proliferation Mitogen-Activated Protein Kinase 1 Gene knockdown Mice Inbred BALB C Mitogen-Activated Protein Kinase 3 Cell growth Kinase Cell cycle medicine.disease Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Cancer research |
| Zdroj: | Molecular carcinogenesis. 58(1) |
| ISSN: | 1098-2744 |
| Popis: | Phosphatidylethanolamine (PE)-binding protein 4 (PEBP4) is an antiapoptotic protein that is aberrantly expressed in various malignancies. We previously demonstrated that PEBP4 expression is dramatically induced in human gliomas and positively correlated with tumor grade and patient survival. However, the function of PEBP4 in human glioma development and underlying mechanisms remain largely unknown. By stable lentiviral vector-mediated silencing of PEBP4, we examined the effects of PEBP4 knockdown on the growth, apoptosis, and invasion of U251 and U373 human glioma cell lines using MTT, Transwell, colony formation, and flow cytometric assays. We examined the in vivo role of PEBP4 in tumor growth by inoculation of BALB/c nu/nu male mice with PEBP4-deficient U251 and U373 cells. The expression of cell cycle- and apoptosis-related proteins was analyzed by Western blotting and immunostaining. Knockdown of PEBP4 significantly reduced the proliferation and invasion of human glioma cells while inducing cell apoptosis by altering the expression of cell cycle- and apoptosis-related proteins. Mechanistically, PEBP4 knockdown led to activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) pathway, an effect that could be reversed by U0126, a selective inhibitor of MEK1/2 (upstream of ERK1/2), suggesting involvement of ERK1/2 signaling in the regulation of glioma development and progression by PEBP4. We identified PEBP4 as a novel regulator mediating human glioma cell proliferation, invasion, and apoptosis as well as tumor formation and growth. Therefore, PEBP4 may be a potential therapeutic target in human glioma treatment. |
| Databáze: | OpenAIRE |
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