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Article

MMP14 Contributes to HDAC Inhibition-Induced Radiosensitization of Glioblastoma

Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China
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Authors to whom correspondence should be addressed.
Academic Editor: Tianhua Niu
Int. J. Mol. Sci. 2021, 22(19), 10403; https://doi.org/10.3390/ijms221910403
Received: 22 July 2021 / Revised: 21 September 2021 / Accepted: 22 September 2021 / Published: 27 September 2021
(This article belongs to the Section Molecular Informatics)
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. View Full-Text
Keywords: GBM; MMP14; radioresistance; HDAC inhibitor; SAHA; bioinformatic analysis; RNA-seq; ChIP-seq GBM; MMP14; radioresistance; HDAC inhibitor; SAHA; bioinformatic analysis; RNA-seq; ChIP-seq
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MDPI and ACS Style

Zhou, Y.; Liu, H.; Zheng, W.; Chen, Q.; Hu, S.; Pan, Y.; Bai, Y.; Zhang, J.; Shao, C. MMP14 Contributes to HDAC Inhibition-Induced Radiosensitization of Glioblastoma. Int. J. Mol. Sci. 2021, 22, 10403. https://doi.org/10.3390/ijms221910403

AMA Style

Zhou Y, Liu H, Zheng W, Chen Q, Hu S, Pan Y, Bai Y, Zhang J, Shao C. MMP14 Contributes to HDAC Inhibition-Induced Radiosensitization of Glioblastoma. International Journal of Molecular Sciences. 2021; 22(19):10403. https://doi.org/10.3390/ijms221910403

Chicago/Turabian Style

Zhou, Yuchuan, Hongxia Liu, Wang Zheng, Qianping Chen, Songling Hu, Yan Pan, Yang Bai, Jianghong Zhang, and Chunlin Shao. 2021. "MMP14 Contributes to HDAC Inhibition-Induced Radiosensitization of Glioblastoma" International Journal of Molecular Sciences 22, no. 19: 10403. https://doi.org/10.3390/ijms221910403

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