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Upregulation of miR-96 promotes radioresistance in glioblastoma cells via targeting PDCD4.
- Source :
-
International journal of oncology [Int J Oncol] 2018 Oct; Vol. 53 (4), pp. 1591-1600. Date of Electronic Publication: 2018 Jul 23. - Publication Year :
- 2018
-
Abstract
- Glioblastoma multiforme (GBM) is the most deadly brain tumor, and it is characterized by extremely poor therapeutic response and overall survival. Adjuvant radiotherapy remains the standard of care following surgical resection. Thus, elucidating the mechanisms conferring radioresistance in GBM is extremely urgent. In the present study, miR-96 was demonstrated to be significantly upregulated in radioresistant GBM cells. Knockdown of miR-96 in the radioresistant GBM cells T98G elevated the % of apoptotic cells and reduced their clonogenic formation ability following radiotherapy. By contrast, overexpression of miR-96 in the radiosensitive GBM cells U87-MG reduced the % of apoptotic cells and increased their clonogenic formation ability following radiotherapy. Results from phosphorylated-H2A histone family member X (γH2AX) foci staining and comet assays revealed that miR-96 enhanced the DNA repair processes. Furthermore, miR-96 overexpression conferred radioresistance by downregulating programmed cell death protein 4 (PDCD4). Luciferase assay results revealed that miR-96 bound to the 3'UTR of PDCD4 mRNA. Finally, U87-MG cells regained radiosensitivity following PDCD4 overexpression. Taken together, the present is the first study to establish that upregulation of miR-96 in GBM cells confers radioresistance via targeting PDCD4, which might be a potential therapeutic target for GBM.
- Subjects :
- 3' Untranslated Regions genetics
Apoptosis genetics
Apoptosis radiation effects
Apoptosis Regulatory Proteins metabolism
Brain Neoplasms genetics
Cell Line, Tumor
DNA Repair genetics
DNA Repair radiation effects
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Glioblastoma genetics
Humans
MicroRNAs genetics
RNA, Messenger genetics
RNA-Binding Proteins metabolism
Up-Regulation
Apoptosis Regulatory Proteins genetics
Brain Neoplasms radiotherapy
Glioblastoma radiotherapy
MicroRNAs metabolism
RNA-Binding Proteins genetics
Radiation Tolerance genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2423
- Volume :
- 53
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International journal of oncology
- Publication Type :
- Academic Journal
- Accession number :
- 30066909
- Full Text :
- https://doi.org/10.3892/ijo.2018.4498