Abstract
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.
Highlights
Glioma is a commonly diagnosed malignant cancer that show poor prognosis and low survival rate
TAZ is upregulated in TNF-related apoptosis-inducing ligand (TRAIL)-resistant glioma cells
We showed that IC50 of TRAIL to U87/R was 7.67 fold higher than its parental U87 cell line
Summary
Glioma is a commonly diagnosed malignant cancer that show poor prognosis and low survival rate. For the advanced glioma patients, systemic chemotherapy is indispensable [1,2,3]. Drug resistance is still a major problem in the chemotherapy of various cancers, including glioma [4, 5]. It is urgent to take strategies to overcome the chemoresistance of glioma. TNF-related apoptosis-inducing ligand (TRAIL) belongs to the member of the TNF superfamily. It triggers caspase-8 and induces extrinsic and intrinsic apoptosis. TRAILcaused extrinsic apoptosis is induced by activation of caspase-8 directly, whereas the intrinsic apoptosis pathway is required the mediation of mitochondria damage [6, 7]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.