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Nucleic Acids Res. 2017 Jun 2;45(10):5930-5944. doi: 10.1093/nar/gkx317.

Identification of miRNA-7 by genome-wide analysis as a critical sensitizer for TRAIL-induced apoptosis in glioblastoma cells.

Author information

1
The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
2
Department of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
3
The State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
4
Department of Radiological Medicine, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
5
The State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
6
The State Key Laboratory of Cancer Biology, Department of Immunology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

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.

PMID:
28459998
PMCID:
PMC5449600
DOI:
10.1093/nar/gkx317
[Indexed for MEDLINE]
Free PMC Article

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