Li Ning, Deng Limei, Zhang Yuming, Tang Xilian, Lei Bingxi, Zhang Qingyu
Department of Hematology Affiliated Hospital of Guangdong Medical University Zhanjiang Guangdong China.
The Marine Biomedical Research Institute Guangdong Medical University Zhanjiang China.
Ibrain. 2024 Mar 11;10(1):19-33. doi: 10.1002/ibra.12150. eCollection 2024 Spring.
Glioma, a malignant brain tumor originating from neural glial cells, presents significant treatment challenges. However, the underlying mechanisms of glioma development are not fully understood, and effective targets are lacking. This study provides insights into the role of insulin-like growth factor 2 messenger RNA-binding protein 2 (IGF2BP2) in glioma progression and its therapeutic potential. Our analysis illustrated that elevated IGF2BP2 expression associated with significantly shorter survival among patients with low-grade glioma (LGG) in The Cancer Genome Atlas (TCGA) database. IGF2BP2 depletion led to compromised cell viability, G0/G1 phase arrest, and reduced colony-formation ability. Furthermore, ultrastructural analysis and mCherry-GFP-LC3 reporter assay revealed an increased abundance of autophagosomes upon IGF2BP2 knockdown. Western blot analysis corroborated these findings by showing reduced p62 levels coupled with increased LC3-ІІ/LC3-I ratio upon IGF2BP2 knockdown. A multicolor immunohistochemistry assay demonstrated the positive correlation between IGF2BP2 and p62 expression in glioma patient samples. Additionally, our analysis suggested a link between IGF2BP2 expression and drug-resistant markers in TCGA-LGG samples, and Cell Counting Kit-8 cell viability assay revealed that knockdown of IGF2BP2 sensitized cells to temozolomide treatment. This comprehensive exploration unveils the role of IGF2BP2 in glioma progression, shedding light on autophagy modulation and chemosensitization strategies for glioma therapy.
胶质瘤是一种起源于神经胶质细胞的恶性脑肿瘤，带来了重大的治疗挑战。然而，胶质瘤发生发展的潜在机制尚未完全明确，且缺乏有效的治疗靶点。本研究深入探讨了胰岛素样生长因子2信使核糖核酸结合蛋白2（IGF2BP2）在胶质瘤进展中的作用及其治疗潜力。我们的分析表明，在癌症基因组图谱（TCGA）数据库中，低级别胶质瘤（LGG）患者中IGF2BP2表达升高与显著缩短的生存期相关。IGF2BP2缺失导致细胞活力受损、G0/G1期阻滞以及集落形成能力降低。此外，超微结构分析和mCherry-GFP-LC3报告基因检测显示，IGF2BP2敲低后自噬体丰度增加。蛋白质免疫印迹分析证实了这些发现，显示IGF2BP2敲低后p62水平降低，同时LC3-II/LC3-I比值增加。多色免疫组织化学检测证明了胶质瘤患者样本中IGF2BP2与p62表达之间呈正相关。此外，我们的分析表明TCGA-LGG样本中IGF2BP2表达与耐药标志物之间存在联系，细胞计数试剂盒-8细胞活力检测显示，敲低IGF2BP2可使细胞对替莫唑胺治疗敏感。这一全面的探索揭示了IGF2BP2在胶质瘤进展中的作用，为胶质瘤治疗的自噬调节和化学增敏策略提供了思路。
