TUFM Promotes Glioblastoma Oncogenesis And Progression Through The MAPK/ERK Signaling Pathway

Mitochondrial Tu translation elongation factor（TUFM）is a key factor in the translational expression of mitochondrial DNA,plays an important role in the control of mitochondrial function.There is evidence that TUFM is involved in tumor oncogenesis and prognosis,but the mechanism of TUFM on tumor remains unclear.The present study aims to the role of TUFM in the occurrence and development of glioblastoma.Through bioinformatics and clinical expression analysis to study the relationship between TUFM expression level and prognosis of TUFM in GBM,predict the possible function of TUFM in mitochondria.Use molecular biology and cell biology methods to study the malignant biological behavior of TUFM on glioblastoma cells and the molecular mechanism that promotes the cell proliferation of glioblastoma cells.Our study has shown that TUFM is highly expressed in GBM,and is associated with poor prognosis.Further detection of the expression of glioblastoma clinical tissues by WB and immunohistochemistry chip also showed that the expression level of TUFM in the clinical tissues of glioblastoma was significantly higher than that of adjacent tissues.At the same time,TUFM knockdown and overexpression glioblastoma cell models were constructed.The study found that overexpression of TUFM promotes the proliferation,migration and invasion of glioblastoma cells,and promotes tumor formation in nude mice.Mitochondrial function test found that TUFM can promote the increase of protein expression of mitochondrial coding genes COX Ⅰ,COX Ⅳ and ND1 in T98 G cells,increase of cell mitochondrial membrane potential,decrease of ROS level,and increase of ATP content.And the study found that the overexpression of TUFM also promoted the increase of KRAS,p-RAF,p-MEK1/2,p-ERK,p-MSK1,p-P90 RSK and p-AMPK protein expression.We speculate that TUFM can increase cell oxidative phosphorylation activity and ATP levels by promoting the expression of mitochondrial-encoded gene proteins in glioblastoma cells.ATP acts as a signal molecule to activate the MAPK/ERK signaling pathway to promote the proliferation of glioblastoma cells.This study helps to reveal the relationship between the regulation of mitochondrial gene expression and oxidative phosphorylation activity and the malignant biological behavior of glioblastoma cells,and lays the foundation for the search for new therapeutic target molecules in the clinical treatment of glioblastoma.