Hsa_circ_0072309 enhances autophagy and TMZ sensitivity in glioblastoma. (25th February 2022)

• Record Type: Journal Article
• Authors: Yuan, Fanen; Zhang, Si; Sun, Qian; Ye, Liguo; Xu, Yang; Xu, Zhou; Deng, Gang; Zhang, Shenqi; Liu, Baohui; Chen, Qianxue
• Is Part Of: CNS neuroscience & therapeutics. Volume 28:Number 6(2022)
• Page Start: 897
• Page End: 912
• Publication Date: 2022-02-25
• Subjects: autophagy -- circRNA -- glioblastoma -- temozolomide; Neuropharmacology -- Periodicals; Central nervous system -- Diseases -- Effect of drugs on -- Periodicals; 612.8
• DOI: 10.1111/cns.13821
• Languages: English
• ISSNs: 1755-5930

Abstract

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 : Yuan et al. describe a function of hsa_circ_0072309 promoting autophagy by p53 signaling pathway and enhancing TMZ sensitivity in p53 wild‐type GBM, but not in p53 mutant GBM. Hsa_circ_0072309 inhibits p53 ubiquitination and increases the stability of p53 protein. MiR‐100 mediates hsa_circ_0072309 regulating p53. P53 inhibitor or autophagy inhibitor could reverse the effect of hsa_circ_0072309 on TMZ sensitivity.