Research Paper Volume 11, Issue 9 pp 2670—2680
Downregulation of miR-125b promotes resistance of glioma cells to TRAIL through overexpression of Tafazzin which is a mitochondrial protein
- 1 Department of Neurosurgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hu’nan Province, China
received: March 9, 2019 ; accepted: April 24, 2019 ; published: May 5, 2019 ;https://doi.org/10.18632/aging.101939
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Copyright: Ma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Overexpression of Tafazzin (TAZ), a mitochondrial protein, is often observed in many cancers. However, the association between aberrant expression of TAZ and drug resistance remains unclear. The aim of this study is to explore the role of TAZ in regulating the TRAIL resistance in glioma. We thus established the TRAIL resistance models on glioma by using the U87 and U251 cell lines (U87/R and U251/R). As the results, obvious overexpression of TAZ was observed in U87/R and U251/R cells. However, knockdown of TAZ increased the sensitivity of U87/R and U251/R cells to TRAIL-induced apoptosis. By contrast, expression of miR-125b was downregulated in U87/R and U251/R cells compared to the parental U87 and U251 cells. Furthermore, decrease of miR-125b was responsible for overexpression of TAZ, because the results of dual-luciferase reporter assays verified that TAZ was targeted by miR-125b. We then showed that enforced expression of miR-125b resensitized the U87/R and U251/R cells to TRAIL-dependent damage of mitochondria and activation of caspase-9 and -3. We demonstrated that overexpression of TAZ caused by downregulation of miR-125b promoted resistance of glioma cells to TRAIL. MiR-125b/TAZ axis may represent a potential strategy to reverse the TRAIL in glioma.