We previously observed that reduced NESG1 protein levels were inversely associated with lymph node metastasis and clinical stage of NPC which suggested its downregulation favored the development of NPC. However, due to the limited patient sample size and the absence of clinical prognosis information, we did not investigate the detailed correlation of NESG1 expression with clinical features and prognosis of NPC. In this report, we used a larger cohort of 204 patients with clinical prognosis information to analyze this relationship. Similar to our previous results, we found that decreased expression of NESG1 inversely correlated with lymph node metastasis and clinical stage of NPC. We further observed that decreased NESG1 expression was correlated with distant metastases and statistically lower in the M1 group compared to the M0 group. Together these studies suggest downregulated NESG1 levels play an unfavorable role in NPC pathogenesis, a correlation which has not been previously reported. Our investigation provides data that reduced NESG1 protein expression is correlated with decreased NPC patient overall survival. According to univariate analyses, overall survival was significantly correlated with age, TNM classification, and NESG1 expression. Multivariate analyses showed that decreased expression of NESG1 alone could be a significant predictor of poor prognosis for NPC patients. Our data are the first to report the clinical significance of decreased NESG1 expression as an unfavorable prognosis TWS119 GSK-3 inhibitor biomarker in NPC. In a prior study, NESG1 overexpression had been observed to suppress cell proliferation, migration, invasion, and cell cycle progression, thus we further examined the biological functions of NESG1 in NPC. We used a loss-of-function approach to knock down the overexpressed NESG1 in 2F4 NPC cells, and confirmed its role in promoting cell proliferation, migration, and invasion in vitro. These results are consistent with our previous investigation. Our studies strongly suggest a suppressive role of NESG1 in the development of NPC. To fully understand the molecular mechanism of NESG1- mediated suppressive pathways in NPC, we analyzed differential expression of NESG1-regulated genes against the pathway-collected database KEGG. Our computational pathway analysis of 1442 differentially expressed genes strongly supported that multiple biological signaling pathways were involved in NESG1-mediated NPC oncogenesis including MAPK, insulin, actin cytoskeleton, focal adhesion, and cell cycle progression. In our recent report, NESG1 altered expression of cell cycle regulators CCNA1 and p21, a finding we confirmed through an inverse approach. We found that inhibition of NESG1 could markedly restore expression of cell cycle promoting CCNA1 while downregulating tumor suppressor p21. Including cell proliferation, differentiation migration, and invasion. MAPK was considered to be an important pathway regulated by NESG1 based on its ranking after computer analysis. Real-time PCR was used to validate the diffe
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