Glioma is one of the lethal central nervous system tumors.The infiltrative and invasive growth nature makes it difficult to identify the boundary between glioma and the normal tissues,resulting in inevitable recurrenc...Glioma is one of the lethal central nervous system tumors.The infiltrative and invasive growth nature makes it difficult to identify the boundary between glioma and the normal tissues,resulting in inevitable recurrence after surgery operation.Gliomas do not metastasize,so to prevent the residual tumor from proliferating or invading is a key challenge.Previous report indicated that hypotaurine could facilitate glioma invasion and suppress demethylases’activities.Using a hypotaurine synthesis deficient U251 cell line,we proved that the cells invasion ability was impaired.Gene expression profile analysis exhibited that knocking down one of the key enzymes of hypotaurine synthesis,2-aminoethanethiol dioxygenase(ADO),significantly affected the extracellular matrix-receptor process.Of that process,Wnt5a expression was severely upregulated by decreased intracellular ADO expression.Cells cultured at the presence of hypotaurine showed a decrease in intracellular Wnt5a protein and mRNA levels.This phenotype was due to hypermethylation of Wnt5a promoter,which was most likely the result of hypotaurine’s inhibiting demethylases activities.Collectively,this study demonstrated that hypotaurine synthesis deficient U251 cells were prone to epigenetic modification and Wnt5a seemed to be a tumor suppressor under that circumstance.This tumor suppression effect is warranted to be reevaluated in real tumor samples and the relevant evidence might contribute to develop new glioma interference strategies.展开更多
基金supported by New and Old Energy Conversion Project of Jining City(2017ZDGH031)Guiding funds for the development of local science and technology by the Central government(2017106014)Natural Science Foundation of Liaoning Province(L2015317).
文摘Glioma is one of the lethal central nervous system tumors.The infiltrative and invasive growth nature makes it difficult to identify the boundary between glioma and the normal tissues,resulting in inevitable recurrence after surgery operation.Gliomas do not metastasize,so to prevent the residual tumor from proliferating or invading is a key challenge.Previous report indicated that hypotaurine could facilitate glioma invasion and suppress demethylases’activities.Using a hypotaurine synthesis deficient U251 cell line,we proved that the cells invasion ability was impaired.Gene expression profile analysis exhibited that knocking down one of the key enzymes of hypotaurine synthesis,2-aminoethanethiol dioxygenase(ADO),significantly affected the extracellular matrix-receptor process.Of that process,Wnt5a expression was severely upregulated by decreased intracellular ADO expression.Cells cultured at the presence of hypotaurine showed a decrease in intracellular Wnt5a protein and mRNA levels.This phenotype was due to hypermethylation of Wnt5a promoter,which was most likely the result of hypotaurine’s inhibiting demethylases activities.Collectively,this study demonstrated that hypotaurine synthesis deficient U251 cells were prone to epigenetic modification and Wnt5a seemed to be a tumor suppressor under that circumstance.This tumor suppression effect is warranted to be reevaluated in real tumor samples and the relevant evidence might contribute to develop new glioma interference strategies.
