Hsa_circ_0072309 enhances autophagy and TMZ sensitivity in glioblastoma

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.