Silencing of telomere-binding protein adrenocortical dysplasia (ACD) homolog enhances radiosensitivity in glioblastoma cells
| Autor: | Francesca Polito, Valeria Barresi, Antonino Germanò, Maria Cucinotta, Chiara Tomasello, M'hammed Aguennouz, Flavio F. Angileri, Stefano Pergolizzi, Rosamaria Di Giorgio, Alfredo Conti, A. Brogna, Rosaria Viola Abbritti, Domenico La Torre |
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| Přispěvatelé: | Polito, Francesca, Cucinotta, Maria, Abbritti, Rosaria V., Brogna, Anna), Pergolizzi, Stefano, Tomasello, Chiara, Barresi, Valeria, Angileri, Flavio, Di Giorgio, Rosamaria, Conti, Alfredo, La Torre, Domenico, Germano, Antonino, Aguennouz, M'Hammed |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Telomerase Cell Survival Telomere-Binding Proteins Brain Neoplasms Caspase 3 Cell Line Tumor Cyclin D1 Glioblastoma Humans Neoplasm Grading Neuronal Apoptosis-Inhibitory Protein Gene Silencing Radiation Tolerance Public Health Environmental and Occupational Health Biochemistry (medical) Physiology (medical) Biology Shelterin Complex Cell Line Brain Neoplasm radio-sensitivity 03 medical and health sciences ACD telomere glioma radiotherapy 0302 clinical medicine Glioma Radioresistance medicine Gene silencing Telomerase reverse transcriptase Clonogenic assay Tumor Telomere-Binding Protein Environmental and Occupational Health General Medicine medicine.disease Telomere 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Public Health Human |
| Popis: | Adrenocortical dysplasia (ACD) is a shelterin protein involved in the maintenance of telomere length and in cancer radioresistance. This study investigated the expression profile of ACD in human gliomas and its role in radioresistance of glioma cells. The expression of ACD was analyzed in 62 different grades of glioma tissues and correlated with prognosis. A radioresistant cell line was generated from U87MG cells. For mechanistic studies, ACD was inhibited by small interfering RNA-targeting ACD and the effect on cell radioresistance, telomerase activity, cyclinD1, caspase-3, hTERT, and BIRC1 was evaluated. Clonogenic assay was performed after irradiation, to investigate the effect of ACD silencing on radiation sensitivity. ACD expression appeared strongly upregulated in higher grade gliomas, and its expression was significantly correlated to grading and poor prognosis. In glioma cell lines, ACD expression pattern was similar to those observed in glioma tissues. In irradiated cells, ACD expression was increased in an ionizing radiation dose-dependent manner. A higher expression of ACD was observed in the radioresistant clones than parental cells. Silencing of ACD led to the enhanced radiation sensitivity, decreased telomerase activity and cyclin D1 expression, reduced expression of BIRC1, and finally to the upregulation of caspase-3. This study represents the first report, which demonstrated the expression pattern of ACD in gliomas and its prognostic value. Our results suggested that ACD is involved in glioblastoma radioresistance, likely through the modulation of telomerase activity, proliferation, and apoptosis. ACD might represent a potential molecular biomarker and a novel therapeutic target in glioblastoma. |
| Databáze: | OpenAIRE |
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