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Identification of miRNA-7 by genome-wide analysis as a critical sensitizer for TRAIL-induced apoptosis in glioblastoma cells.
- Source :
-
Nucleic acids research [Nucleic Acids Res] 2017 Jun 02; Vol. 45 (10), pp. 5930-5944. - Publication Year :
- 2017
-
Abstract
- Glioblastoma (GBM) is still one of the most lethal forms of brain tumor despite of the improvements in treatments. TRAIL (TNF-related apoptosis-inducing ligand) is a promising anticancer agent that can be potentially used as an alternative or complementary therapy because of its specific antitumor activity. To define the novel pathways that regulate susceptibility to TRAIL in GBM cells, we performed a genome-wide expression profiling of microRNAs in GBM cell lines with the distinct sensitivity to TRAIL-induced apoptosis. We found that the expression pattern of miR-7 is closely correlated with sensitivity of GBM cells to TRAIL. Furthermore, our gain and loss of function experiments showed that miR-7 is a potential sensitizer for TRAIL-induced apoptosis in GBM cells. In the mechanistic study, we identified XIAP is a direct downstream gene of miR-7. Additionally, this regulatory axis could also exert in other types of tumor cells like hepatocellular carcinoma cells. More importantly, in the xenograft model, enforced expression of miR-7 in TRAIL-overexpressed mesenchymal stem cells increased apoptosis and suppressed tumor growth in an exosome dependent manner. In conclusion, we identify that miR-7 is a critical sensitizer for TRAIL-induced apoptosis, thus making it as a promising therapeutic candidate for TRAIL resistance in GBM cells.<br /> (© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Subjects :
- Animals
Apoptosis genetics
Brain Neoplasms genetics
Cell Line, Tumor
Exosomes genetics
Gene Expression Profiling
Gene Transfer Techniques
Genome-Wide Association Study
Glioblastoma genetics
HEK293 Cells
Hep G2 Cells
Humans
Male
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells metabolism
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs administration & dosage
MicroRNAs biosynthesis
MicroRNAs therapeutic use
RNA administration & dosage
RNA therapeutic use
RNA, Neoplasm administration & dosage
RNA, Neoplasm biosynthesis
RNA, Neoplasm therapeutic use
TNF-Related Apoptosis-Inducing Ligand administration & dosage
TNF-Related Apoptosis-Inducing Ligand therapeutic use
X-Linked Inhibitor of Apoptosis Protein physiology
Xenograft Model Antitumor Assays
Apoptosis physiology
Brain Neoplasms pathology
Gene Expression Regulation, Neoplastic
Glioblastoma pathology
MicroRNAs genetics
Neoplasm Proteins physiology
RNA, Neoplasm genetics
TNF-Related Apoptosis-Inducing Ligand physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1362-4962
- Volume :
- 45
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Nucleic acids research
- Publication Type :
- Academic Journal
- Accession number :
- 28459998
- Full Text :
- https://doi.org/10.1093/nar/gkx317