Department of Neurosurgery, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518020, China.
Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
Cancer Biol Med. 2020 Feb 15;17(1):112-131. doi: 10.20892/j.issn.2095-3941.2019.0164.
Temozolomide (TMZ) is commonly used for glioblastoma multiforme (GBM) chemotherapy. However, drug resistance limits its therapeutic effect in GBM treatment. RNA-binding proteins (RBPs) have vital roles in posttranscriptional events. While disturbance of RBP-RNA network activity is potentially associated with cancer development, the precise mechanisms are not fully known. The gene, encoding small nuclear ribonucleoprotein polypeptide G, was recently found to be related to cancer incidence, but its exact function has yet to be elucidated. knockdown was achieved via short hairpin RNAs. Gene expression profiling and Western blot analyses were used to identify potential glioma cell growth signaling pathways affected by . Xenograft tumors were examined to determine the carcinogenic effects of on glioma tissues. The -mediated inhibitory effect on glioma cells might be due to the targeted prevention of Myc and p53. In addition, the effects of loss on p53 levels and cell cycle progression were found to be Myc-dependent. Furthermore, was increased in TMZ-resistant GBM cells, and downregulation of potentially sensitized resistant cells to TMZ, suggesting that deficiency decreases the chemoresistance of GBM cells to TMZ via the p53 signaling pathway. Our data confirmed that suppression sensitizes GBM cells to TMZ by targeting Myc via the p53 signaling cascade. These results indicated that is a probable molecular target of GBM and suggested that suppressing in resistant GBM cells might be a substantially beneficial method for overcoming essential drug resistance.
替莫唑胺（TMZ）常用于多形性胶质母细胞瘤（GBM）的化疗。然而，药物耐药性限制了其在 GBM 治疗中的疗效。RNA 结合蛋白（RBPs）在转录后事件中发挥着重要作用。虽然 RBP-RNA 网络活性的紊乱可能与癌症的发生有关，但确切的机制尚不完全清楚。 基因，编码小核核糖核蛋白多肽 G，最近被发现与癌症的发生有关，但它的确切功能尚未阐明。 通过短发夹 RNA 实现敲低。基因表达谱和 Western blot 分析用于鉴定受 影响的潜在神经胶质瘤细胞生长信号通路。 研究异种移植肿瘤，以确定 对神经胶质瘤组织的致癌作用。 对神经胶质瘤细胞的抑制作用可能是由于靶向预防 Myc 和 p53 所致。此外，发现 缺失对 p53 水平和细胞周期进展的影响依赖于 Myc。此外，TMZ 耐药性 GBM 细胞中 增加，下调 可能使耐药细胞对 TMZ 敏感，表明 缺乏通过 p53 信号通路降低 GBM 细胞对 TMZ 的化疗耐药性。我们的数据证实， 通过 p53 信号级联靶向 Myc 抑制可使 GBM 细胞对 TMZ 敏感。 这些结果表明 是 GBM 的一个可能的分子靶点，并表明抑制耐药性 GBM 细胞中的 可能是克服关键药物耐药性的一种非常有益的方法。
