Regulation Of MCT1 On Invasion And Glucose Metabolism Of Bladder Cancer

Objective: Monocarboxylate transporter 1(MCT1)is an important factor mediating lactate transport.Because of the Warburg effect,cancer cells generate energy by converting glucose to lactic acid even in oxygen-rich environments.The production and clearance of lactic acid is an important signal transduction pathway for cancer cell metabolism.Recent studies have shown that MCT1 plays an important carcinogenic role in the development of cancer cells.High expression of MCT1 has been found in tumors of different systems,and its expression is closely related to the malignant degree of tumors.At the same time,the process of epithelial-mesenchymal transition plays an important role in a series of complex processes,such as the progression and metastasis of cancer cells in various systems.The process of epithelial-mesenchymal transition is related to the metastasis of bladder cancer cells and the generation of drug resistance.Bladder cancer is a common malignant tumor of urinary system which threatens people's health.Although the treatment methods are improving,the long-term prognosis of patients with bladder cancer is not ideal.The main purpose of this study is to analyze the relationship between the expression of MCT1 in bladder cancer and the prognosis of other patients,and to analyze the effect of MCT1 on the proliferation,migration and invasion of bladder cancer cells,and to analyze the mechanism of MCT1 in bladder cancer cells and its regulation on sugar metabolism of bladder cancer.Methods: The purpose of this study was to investigate the expression of MCT1 in bladder cancer cells and its role.We selected 124 cases of bladder cancer tissues and studied the expression of MCT1 by immunohistochemical staining.We compared the expression of MCT1 in patients with or without lymphatic metastasis.By detecting the expression of MCT1,patients were divided into MCT1 high expression group and MCT1 low expression group.By analyzing the prognosis of the two groups,the relationship between the expression of MCT1 and the prognosis of bladder cancer patients was analyzed.We also used the Cancer Genome Mapping Database(TCGA database)to select426 patients and explored the relationship between MCT1 and the prognosis of bladder cancer through the same grouping study.The expression of MCT1 in bladder cancer cells was down-regulated by siRNA transfection.The effect of down-regulation of MCT1 expression on the proliferation of bladder cancer cells was studied by CCK8 method and in vivo oncogenesis experiment.The effect of down-regulation of MCT1 expression on the migration of bladder cancer cells in vitro was analyzed by scratch test.Finally,the effect of down-regulation of MCT1 expression on bladder cancer cells was analyzed by Transwell experiment.The effect of invasion in vitro.The effects of hypoxia on the expression of MCT1 and.HIF-1? and the transport of lactic acid were also analyzed.The effect of down-regulation of MCT1 on aerobic glycolysis of bladder cancer cells and its relationship with HIF-1? were emphatically analyzed by Western blot.Results: This study found that the expression of MCT1 in bladder cancer cells with lymph node metastasis(P = 0.022)and distant metastasis(P = 0.005)was higher than that in patients without lymph node metastasis and distant metastasis.By comparing the expression of MCT1 in 124 patients with the total survival time,it was found that the survival time of patients with high expression of MCT1 was significantly lower than that of patients with low expression of MCT1(P < 0.001).By down-regulating the expression of MCT1 gene,CCK8 assay and tumorigenesis experiment in vivo,it was found that down-regulating the expression of MCT1 significantly inhibited the proliferation of bladder cancer cells.Scratch assay showed that down-regulation of MCT1 expression significantly inhibited the migration of bladder cancer cells.Transwell assay showed that down-regulation of MCT1 expression in bladder cancer cells significantly inhibited the invasion of bladder cancer cells.Inhibition of MCT1 expression in bladder cancer cells inhibited the process of epithelial-mesenchymal transition,increased the expression of E-cadherin,and decreased the expression of N-cadherin,vimentin and Snail.The down-regulation of MCT1 expression can reduce the level of lactic acid in cell culture medium,and the expression of HK2,GLUT1 and LDHB equal to glycolysis-related genes.At the same time,MCT1 is partially dependent on the expression of HIF-1a gene.Hypoxic environment can increase the expression of MCT1 and HIF-1?,and inhibit the expression of HIF-1?.It can be found that the expression of MCT1 is closely related to the glycometabolism of cancer cells.Conclusions: 1.The high expression of MCT1 is closely related to the poor prognosis of bladder cancer patients.2.After down-regulation of MCT1 expression,the proliferation,invasion and migration of bladder cancer cells were weakened.3.MCT1 could affect the glycometabolism of bladder cancer cells.4.MCT1 may affect the progression and metastasis of bladder cancer by affecting epithelial-mesenchymaltransition and aerobic glycolysis.