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

Yulong Lan, Jiacheng Lou, Jiliang Hu, et al.

Abstract


Objective: Temozolomide (TMZ) is commonly used for glioblastoma multiforme (GBM) chemotherapy. However, drug resistancelimits its therapeutic effect in GBM treatment. RNA-binding proteins (RBPs) have vital roles in posttranscriptional events. Whiledisturbance of RBP-RNA network activity is potentially associated with cancer development, the precise mechanisms are not fullyknown. The SNRPG gene, encoding small nuclear ribonucleoprotein polypeptide G, was recently found to be related to cancerincidence, but its exact function has yet to be elucidated.

Methods: SNRPG knockdown was achieved via short hairpin RNAs. Gene expression profiling and Western blot analyses were usedto identify potential glioma cell growth signaling pathways affected by SNRPG. Xenograft tumors were examined to determine thecarcinogenic effects of SNRPG on glioma tissues.

Results: The SNRPG-mediated inhibitory effect on glioma cells might be due to the targeted prevention of Myc and p53. In addition,the effects of SNRPG loss on p53 levels and cell cycle progression were found to be Myc-dependent. Furthermore, SNRPG wasincreased in TMZ-resistant GBM cells, and downregulation of SNRPG potentially sensitized resistant cells to TMZ, suggesting thatSNRPG deficiency decreases the chemoresistance of GBM cells to TMZ via the p53 signaling pathway. Our data confirmed thatSNRPG suppression sensitizes GBM cells to TMZ by targeting Myc via the p53 signaling cascade.

Conclusions: These results indicated that SNRPG is a probable molecular target of GBM and suggested that suppressing SNRPG inresistant GBM cells might be a substantially beneficial method for overcoming essential drug resistance.

Cite this article as: Lan Y, Lou J, Hu J, Yu Z, Lyu W, Zhang B. A powerful HUPANon a pan-genome study: significance and perspectives. Cancer Biol Med. 2020;17: 112-131. doi: 10.20892/j.issn.2095-3941.2019.0164


Keywords


SNRPG; glioblastoma; cell cycle; temozolomide; therapy

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