期刊
MOLECULAR THERAPY-NUCLEIC ACIDS
卷 8, 期 -, 页码 482-492出版社
CELL PRESS
DOI: 10.1016/j.omtn.2017.07.015
关键词
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资金
- National Natural Science Foundation of China [81372450]
- PhD Start-up Fund of Natural Science Foundation of Guangdong Province [2015A030310139]
- Science and Technology Program of Guangzhou [2014J4100045]
Recombinant tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), as a novel cancer therapeutic, is being tested in phase II and III clinical trials; however, TRAIL resistance remains a big obstacle preventing its clinical application. Considering that TRAIL-induced apoptosis through death receptors DR4 and DR5, their activation may be an alternative pathway to suppress TRAIL resistance. In this study, a negative correlation between DR5 expression and TRAIL resistance was observed, and miR-133a was predicted to be the most promising candidate to suppress DR5 expression. Further investigation demonstrated that miR-133a knockdown dramatically suppressed TRAIL resistance in glioblastoma in vitro and in vivo. An NF-kappa B family member, phosphorylated I kappa B alpha a (P-IkB alpha), was shown to be stimulated by miR-133a, leading to the activation of this signaling. Finally, miR-133a was found to be inversely correlated with DR5 expression in human clinical specimens. In conclusion, our data demonstrate that miR-133a promotes TRAIL resistance in glioblastoma by suppressing DR5 expression and activating NF-kappa B signaling.
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