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The Expression And The Biological Functions Of NNMT In Adult Gliomas

Posted on:2017-01-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:J S HanFull Text:PDF
GTID:1224330488467420Subject:Neurosurgery
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Backgroundandpurpose:Glioma, especially glioblastoma (GBM), is one of the most common cause for cancer-related death throughout the world. Despite advances in diagnosis and therapy, the prognosis has not been improved substantially over the past decades. Therefore, effective strategies for precision therapeutic targets are urgently needed.Methodsand Results:In present study, both bioinformatics’ analyses and in vitro functional experiments are performed to explore the prognostic and therapeutic significance of nicotinamide N-methyltransferase (NNMT) in glioma and glioma stem cells (GSCs). Results indicate that NNMT positively correlates with WHO grade and neural stem cells (NSCs) to GSCs transformation. Kaplan□Meier survival curves reveal that high NNMT expression is associated with unfavorable progression□free survivaland overall survival times in patients with glioma. Multivariate analyses further show that NNMT was an independent prognostic marker ofoverall survival. Gene ontology of NNMT significantly related-genes demonstrate that these genes are mainly enriched in immune response, chromatin modification and glioma malignancy. Moreover, exogenous overexpression of NNMT in human glioma cells promotes proliferation and invasion in a great extent. In silico analysis detects that NNMT was associated with chemo-and radio-therapy in GSCs and tightly associated with therapeutic efficiency.Conclusion:All these experimental data suggest that NNMT plays a critical role in progression and tumorigenic capacity of glioma, and its inhibition could represent a potential molecular approach for clinical management.
Keywords/Search Tags:Nicotinamide N-methyltransferase, glioma, glioma stem ceIls, chemotherapy, radiotherapy
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