Department of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, China.
Department of Orthopedics, The Air Force Hospital of Eastern Theater, China.
J Immunol Res. 2022 May 14;2022:5799776. doi: 10.1155/2022/5799776. eCollection 2022.
Glioma is a serious fatal type of cancer with the shorter median survival period and poor quality of living. The overall 5-year survival rate remains low due to high recurrence rates. Glioma stem cells (GSCs) play the important roles in the development of gliomas. Examination of the numerous biomarkers or cancer-associated genes involved in the development or prevention of glioma may therefore serve the discovery of novel strategies to treat patients with glioma. Hypoxia induced by using CoCl application and 14-3-3 protein knockdown by specific small interfering RNA transfection were performed in GSCs both in vitro and in vivo to observe their role in glioma progression and metastasis occurrence by using western blot analysis and MTT assay. The results demonstrated that CoCl application enhanced the 14-3-3 protein expression and mRNA levels via the PIK pathway in GSCs. Furthermore, hypoxia promoted GSC cell proliferation and activated the expression of proliferating cell nuclear antigen, which was inhibited following 14-3-3 knockdown. In addition, tumor growth in mice was enhanced by CoCl application but reversed following 14-3-3 knockdown, which also enhanced GSC cell apoptosis. In conclusion, the present study demonstrated that hypoxia promoted glioma growth both in vitro and in vivo by increasing the 14-3-3 expression via the PIK signaling pathway. 14-3-3 and HIF-1 may therefore be considered as the potential therapeutic target to treat patients with glioma.
神经胶质瘤是一种严重的致命型癌症，其中位生存期较短，生活质量较差。由于高复发率，总体 5 年生存率仍然较低。神经胶质瘤干细胞（GSCs）在神经胶质瘤的发生发展中起重要作用。因此，研究参与神经胶质瘤发生或预防的众多生物标志物或癌相关基因，可能为治疗神经胶质瘤患者发现新的策略。在体外和体内，通过使用 CoCl 应用和特定的小干扰 RNA 转染来敲低 14-3-3 蛋白，观察它们在神经胶质瘤进展和转移发生中的作用，通过 Western blot 分析和 MTT 检测。结果表明，CoCl 通过 PIK 通路增强了 GSCs 中的 14-3-3 蛋白表达和 mRNA 水平。此外，缺氧促进 GSC 细胞增殖，并激活增殖细胞核抗原的表达，而敲低 14-3-3 后则被抑制。此外，CoCl 的应用增强了小鼠肿瘤的生长，但 14-3-3 敲低后则逆转了这一现象，同时也增强了 GSC 细胞的凋亡。总之，本研究表明，缺氧通过 PIK 信号通路增加 14-3-3 的表达，从而促进了体外和体内神经胶质瘤的生长。因此，14-3-3 和 HIF-1 可被视为治疗神经胶质瘤患者的潜在治疗靶点。
