期刊
FRONTIERS IN ONCOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2022.870034
关键词
miRNA; glioblastoma; TRAIL; apoptosis; combination therapy
类别
资金
- National Natural Science Foundation of China
- Science and Technology Department of Shanxi Province, China
- Natural Science Basic Research Project of Shaanxi Province, China
- Natural Science Foundation of Hainan Province, China
- Scientific Research Fund Project of Xijing hospital
- [81773262]
- [81903149]
- [31770909]
- [82173046]
- [2018JC-013]
- [2021SF-058]
- [2020JM-322]
- [819QN377]
- [XJZT19ML39]
MiR-137 increases the sensitivity of GBM cells to TRAIL-induced apoptosis by targeting XIAP. Combined application of miR-137 and TRAIL effectively suppresses tumor growth in a xenograft model.
Glioblastoma (GBM) is the most lethal primary brain tumor in the central nervous system with limited therapeutic strategies to prolong the survival rate in clinic. TNF-related apoptosis-inducing ligand (TRAIL)-based strategy has been demonstrated to induce cell death in an extensive spectrum of tumor cells, including GBM, while a considerable proportion of malignant cells are resistant to TRAIL-induced apoptosis. MiR-137 is highly expressed in the brain, but significantly decreases with advanced progression of GBM. However, the functional link between miR-137 and TRAIL-induced apoptosis in GBM cells has not been established. Here, GBM cells were transfected with miR-137, and gene expression levels were examined by qRT-PCR and western blot. Apoptotic cells were measured by Annexin-V staining and TUNEL assay. Our data showed that miR-137 sensitizes GBM cells to the TRAIL-mediated apoptosis. Mechanistically, we identified that XIAP is a bona fide target of miR-137, which is essential for miR-137-regulated sensitivity of TRAIL-induced cell death in GBM cells. Finally, in a xenograft model, combined utilization of miR-137 and TRAIL potently suppresses tumor growth in vivo. Collectively, we demonstrate that a miR-137-XIAP axis is required for the sensitivity of TRAIL-induced cell death and shed a light on the avenue for the treatment of GBM.
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