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Hsa_circ_0072309 enhances autophagy and TMZ sensitivity in glioblastoma.
- Source :
-
CNS Neuroscience & Therapeutics . Jun2022, Vol. 28 Issue 6, p897-912. 16p. - Publication Year :
- 2022
-
Abstract
- Aims: Circular RNAs have been reported to play key roles in the progression of various cancers, including gliomas. The present study was designed to investigate the role of hsa_circ_0072309 in autophagy and temozolomide (TMZ) sensitivity in glioblastoma (GBM). Methods: The effect of hsa_circ_0072309 on autophagy and TMZ sensitivity were examined by GFP‐RFP‐LC3, transmission electron microscopy(TEM), flow cytometry, Western blot, and immunofluorescence. The mechanism of hsa_circ_0072309 regulating p53 signaling pathway was analyzed using Western blot, IP, and rescue experiments. Results: Low hsa_circ_0072309 expression predicts poor prognosis for glioma patients. The regulation of hsa_circ_0072309 on autophagy and TMZ sensitivity depends on the status of p53. Hsa_circ_0072309 promoted autophagy by p53 signaling pathway and enhanced sensitivity of glioblastoma to temozolomide (TMZ) in p53 wild‐type GBM, but not in p53 mutant GBM. Hsa_circ_0072309 inhibits p53 ubiquitination and increases the stability of p53 protein in the context of p53 wild‐type. MiR‐100 mediates hsa_circ_0072309 regulating p53. P53 inhibitor or autophagy inhibitor could reverse the effect of hsa_circ_0072309 on TMZ sensitivity in p53 wild‐type GBM. Conclusions: This study revealed a function of hsa_circ_0072309 promoting autophagy by p53 signaling pathway and enhancing TMZ sensitivity. These findings demonstrated that hsa_circ_0072309 may be a potential and promising target in designing the treatment strategy for GBM. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17555930
- Volume :
- 28
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- CNS Neuroscience & Therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 156657648
- Full Text :
- https://doi.org/10.1111/cns.13821