Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.
Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.
CNS Neurosci Ther. 2022 Jun;28(6):897-912. doi: 10.1111/cns.13821. Epub 2022 Feb 25.
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).
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.
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.
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.
环状 RNA 已被报道在多种癌症的进展中发挥关键作用，包括神经胶质瘤。本研究旨在探讨 hsa_circ_0072309 在神经胶质瘤自噬和替莫唑胺（TMZ）敏感性中的作用。
通过 GFP-RFP-LC3、透射电子显微镜（TEM）、流式细胞术、Western blot 和免疫荧光法检测 hsa_circ_0072309 对自噬和 TMZ 敏感性的影响。通过 Western blot、IP 和挽救实验分析 hsa_circ_0072309 调节 p53 信号通路的机制。
低 hsa_circ_0072309 表达预示着神经胶质瘤患者的预后不良。hsa_circ_0072309 对自噬和 TMZ 敏感性的调节取决于 p53 的状态。hsa_circ_0072309 通过 p53 信号通路促进自噬，并在 p53 野生型 GBM 中增强对替莫唑胺（TMZ）的敏感性，但在 p53 突变型 GBM 中则不然。hsa_circ_0072309 抑制 p53 泛素化，增加 p53 蛋白在 p53 野生型中的稳定性。miR-100 介导 hsa_circ_0072309 调节 p53。在 p53 野生型 GBM 中，p53 抑制剂或自噬抑制剂可逆转 hsa_circ_0072309 对 TMZ 敏感性的影响。
本研究揭示了 hsa_circ_0072309 通过 p53 信号通路促进自噬并增强 TMZ 敏感性的功能。这些发现表明，hsa_circ_0072309 可能是设计 GBM 治疗策略的一个有潜力和有前途的靶点。
