miR-133a Promotes TRAIL Resistance in Glioblastoma via Suppressing Death Receptor 5 and Activating NF-κB Signaling

• Main Authors: Shan-shan Wang (Author), Lu Feng (Author), Bao-guang Hu (Author), Ying-fei Lu (Author), Wei-mao Wang (Author), Wei Guo (Author), Chun-wai Suen (Author), Bao-hua Jiao (Author), Jian-xin Pang (Author), Wei-ming Fu (Author), Jin-fang Zhang (Author)
• Format: Book
• Published: Elsevier, 2017-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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-κB family member, phosphorylated IκBα (P-IκBα), 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-κB signaling. Keywords: microRNA-133, TRAIL, DR5, NF-κB signaling, glioblastoma multiforme

Item Description

2162-2531
10.1016/j.omtn.2017.07.015