MMP14 Contributes to HDAC Inhibition-Induced Radiosensitization of Glioblastoma
| Autor: | Yuchuan Zhou, Qianping Chen, Wang Zheng, Yang Bai, Chunlin Shao, Yan Pan, Songling Hu, Jianghong Zhang, Hongxia Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
QH301-705.5
Cell Biology Radiation Tolerance GBM Article Catalysis Inorganic Chemistry HDAC inhibitor Cell Line Tumor Glioma Radioresistance Gene expression Matrix Metalloproteinase 14 medicine Humans Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Spectroscopy Vorinostat MMP14 Organic Chemistry SAHA Chemoradiotherapy General Medicine Transfection medicine.disease bioinformatic analysis Neoplasm Proteins Computer Science Applications Histone Deacetylase Inhibitors radioresistance ChIP-seq Chemistry medicine.anatomical_structure Cell culture Cancer research Histone deacetylase RNA-seq Databases Nucleic Acid Glioblastoma |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 19 International Journal of Molecular Sciences, Vol 22, Iss 10403, p 10403 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms221910403 |
| Popis: | Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Radiotherapy has long been an important treatment method of GBM. However, the intrinsic radioresistance of GBM cells is a key reason of poor therapeutic efficiency. Recently, many studies have shown that using the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) in radiotherapy may improve the prognosis of GBM patients, but the underlying molecular mechanisms remain unclear. In this study, Gene Expression Omnibus (GEO) datasets GSE153982 and GSE131956 were analyzed to evaluate radiation-induced changes of gene expression in GBM without or with SAHA treatment, respectively. Additionally, the survival-associated genes of GBM patients were screened using the Chinese Glioma Genome Atlas (CGGA) database. Taking the intersection of these three datasets, 11 survival-associated genes were discovered to be activated by irradiation and regulated by SAHA. The expressions of these genes were further verified in human GBM cell lines U251, T98G, and U251 homologous radioresistant cells (U251R) by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). It was found that MMP14 mRNA was considerably highly expressed in the radioresistant cell lines and was reduced by SAHA treatment. Transfection of MMP14 siRNA (siMMP14) suppressed cell survivals of these GBM cells after irradiation. Taken together, our results reveal for the first time that the MMP14 gene contributed to SAHA-induced radiosensitization of GBM. |
| Databáze: | OpenAIRE |
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