Silencing NUDT21 Attenuates the Mesenchymal Identity of Glioblastoma Cells via the NF-κB Pathway

Abstract

The proneural (PN) and mesenchymal (MES) subtypes of glioblastoma multiforme (GBM) are robust and generally consistent with classification schemes. GBMs in the MES subclass are predominantly primary tumors that, compared to PN tumors, exhibit a worse prognosis; thus, understanding the mechanism of MES differentiation may be of great benefit for the treatment of GBM. Nuclear factor kappa B (NF-κB) signaling is critically important in GBM, and activation of NF-κB could induce MES transdifferentiation in GBM, which warrants additional research. <i>NUDT21</i> is a newly discovered tumor-associated gene according to our current research. The exact roles of <i>NUDT21</i> in cancer incidence have not been elucidated. Here, we report that <i>NUDT21</i> expression was upregulated in human glioma tissues and that <i>NUDT21</i> promoted glioma cell proliferation, likely through the NF-κB signaling pathway. Gene set enrichment analysis, western blotting, and quantitative real-time reverse transcription polymerase chain reaction confirmed that NF-κB inhibitor zeta (NFKBIZ) was a downstream target affected by <i>NUDT21</i> and that the MES identity genes in glioblastoma cells, <i>CHI3L1</i> and <i>FN1</i>, were also differentially regulated. Our results suggest that <i>NUDT21</i> is an upstream regulator of the NF-κB pathway and a potential molecular target for the MES subtype of GBM.