Study On The Role Of MTHFD2 In The Development Of Oral Squamous Cell Carcinoma

Background:Methylenetetrahydrofolate dehydrogenase 2(MTHFD2)is an important mitochondrial folate metabolism regulator enzyme that plays a key role in cellular nucleic acid synthesis and oxidative stress.Highly expressed MTHFD2 is often associated with poor tumor prognosis,and silence or decrease MTHFD2 expression generally inhibits malignant phenotypes,such as tumor cell proliferation,invasion,and migration,and induce tumor cell death.However,the mechanism of MTHFD2 in oral squamous cell carcinoma(OSCC)has not been clarified,so this study will explore the relationship between MTHFD2 and OSCC and its role in OSCC through redox metabolism,which will provide new ideas for future research on targeted drugs for MTHFD2.Methods:By obtaining the expression of MTHFD2 and related prognostic indicators in the TCGA database,the correlation between MTHFD2 and OSCC was analyzed.The relationship between MTHFD2 expression level and clinicopathological characteristics was analyzed by tissue experiments in patients with OSCC in clinical practice.The expression of MTHFD2 in OSCC cell lines and human normal squamous epithelial cells(NOK)was detected,and the OSCC cell line with the highest MTHFD2 expression level was screened for subsequent experiments.OSCC cells were transfected with lentivirus to inhibit the expression of MTHFD2 and study the related biological functions of MTHFD2.The effects of MTHFD2 on OSCC intracellular redox metabolism were studied by detecting the changes of redox indexes such as intracellular reactive oxygen species,nicotinamide adenine dinucleotide phosphate,and glutathione,and the mechanism of action of MTHFD2 affecting OSCC progression by regulating redox was discussed.Results:The database analysis results showed that the expression of MTHFD2 in OSCC samples was higher than that in neighboring healthy control samples,MTHFD2 had relatively high accuracy for diagnosis and prediction of OSCC,and the overall prognosis of OSCC patients with high MTHFD2 expression was poor.The results of clinical histopathological analysis showed that the expression of MTHFD2 in OSCC tissues was higher and correlated with poor TNM staging.MTHFD2 has varying degrees of high expression in several OSCC cell lines,with the highest expression level in CAL27.When the expression of MTHFD2 is inhibited,the biological functions such as proliferation,migration,and invasion of OSCC are weakened,while apoptosis increases.The results showed that inhibition of MTHFD2 expression could inhibit tumor proliferation.In a low-glucose culture environment,inhibition of MTHFD2 expression causes increased intracellular reactive oxygen species levels and decreased nicotinamide adenine dinucleotide phosphate and glutathione levels.Conclusion:In summary,this study found that expression of MTHFD2 was significantly higher in OSCC tissues than in normal tissues adjacent to the cancer.At the same time,it was found that MTHFD2 showed high expression in OSCC cells,and when the expression of MTHFD2 was inhibited,the biological functions such as proliferation,migration and invasion of OSCCs would be weakened,and apoptosis would increase.When intracellular MTHFD2 levels decreased,intracellular reactive oxygen species levels increased and decreased nicotinamide adenine dinucleotide phosphate and glutathione levels decreased,indicating that MTHFD2 can affect OSCC progression by regulating redox metabolism.This provides new ideas and potential targets for us to study the treatment of OSCC in the future.