Downregulation of SNRPG induces cell cycle arrest and sensitizes human glioblastoma cells to temozolomide by targeting Myc through a p53-dependent signaling pathway

Abstract

<b>Objective:</b> 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 <i>SNRPG</i> 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. <b>Methods:</b><i>SNRPG</i> 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 <i>SNRPG</i>. Xenograft tumors were examined to determine the carcinogenic effects of <i>SNRPG</i> on glioma tissues. <b>Results:</b> The <i>SNRPG</i>-mediated inhibitory effect on glioma cells might be due to the targeted prevention of Myc and p53. In addition, the effects of <i>SNRPG</i> loss on p53 levels and cell cycle progression were found to be Myc-dependent. Furthermore, <i>SNRPG</i> was increased in TMZ-resistant GBM cells, and downregulation of <i>SNRPG</i> potentially sensitized resistant cells to TMZ, suggesting that <i>SNRPG</i> deficiency decreases the chemoresistance of GBM cells to TMZ via the p53 signaling pathway. Our data confirmed that <i>SNRPG</i> suppression sensitizes GBM cells to TMZ by targeting Myc via the p53 signaling cascade. <b>Conclusions:</b> These results indicated that <i>SNRPG</i> is a probable molecular target of GBM and suggested that suppressing <i>SNRPG</i> in resistant GBM cells might be a substantially beneficial method for overcoming essential drug resistance.