| BACKGROUD&OBJECTIVE:Prostate cancer is the most common malignancy in men in the world.A large number of gene mutations and chromosomal aberrations have been found in the genomes of prostate cancer patients.Deep understanding of genetics and pathogenesis may significantly improve the treatment and prognosis of prostate cancer.However,many problems such as the contradictory results of prostate cancer research and the difficulties of clinical trials have made the treatment of prostate cancer still severe.There is increasing evidence that metabolic enzymes are involved in the development of tumors independent of their metabolic activity.These evidence show us that the non-metabolic pathway is also an important part of understanding the role of metabolic enzymes in tumor progression.Phosphoglycerate mutase 1(PGAM1)is a glycolytic enzyme,which catalyzes the conversion of 3-phosphoglycerate(3-PG)to 2-phosphoglycerate(3-PG)to carry out aerobic glycolysis.Studies have reported that PGAM1 may promote tumor migration through non-metabolic enzymes.Since exosomes were first discovered,there has been significant progress in research in this field.Exosomes evolved from simple cell "excreta" into a major and critical participant in pathologic(especially tumor metastasis)and normal physiological processes.It was shown that exosomes are involved in a critical autocrine mechanism responsible for directing cell movement and influencing the migration speed of cancer cells.In this study,the function of PGAM1 in the proliferation and migration of prostate cancer cells was studied.Furthermore,the molecular mechanism of PGAM1 to promote the migration of prostate cancer cells via exosomes was discussed.This study is expected to provide a new theoretical basis and molecular marker for metastasis of prostate cancer.METHODS:The effect of PGAM1 on cell proliferation ability was detected by CCK-8 assay,colony formation assay and Xenograft model in nude mice assay.The effect of PGAM1 on cell migration ability was determined by the experiment of scratch wound healing assay and transwell migration assay.Western blot was used to verify the expression of PGAM1 protein in exosomes.Scratch wound healing assay and transwell migration assay was used to detect the ability of cell migration after PGAM1 entering the cell through exosomes in different treatment groups.Western blot was used to verify the effect of PGAM1 on EMT signaling pathway through exosomes.RESULTS:1)The CCK-8 assay,colony formation assay and Xenograft model in nude mice assay results showed that the proliferation ability of PGAM1 over-expression group was significantly higher than that in the control group,and the reverse results were observed in the PGAM1 knockdown group.The scratch wound healing assay and transwell migration assay results showed that the migration ability of PGAM1 over-expression group was significantly higher than that in the control group,and the reverse results were observed in the PGAM1 knockdown group.2)Western blot detected the expression of PGAM1 in prostate cancer exosomes.When the expression of PGAM1 in cells increases,the expression of PGAM1 in exosomes also increases.3)Compared to the control group,after the exosomes derived from PGAM1 over-expression cells were uptake into the cells,the scratch wound healing assay and transwell migration assay results showed that the migration ability of the cells was significantly enhanced.And Western blot results showed that the expression level of E-cadherin and other epithelial markers decreased,the expression level of Vimentin and other mesenchymal markers increased.CONCLUSION:1)Over-expression of PGAM1 can enhance the proliferation and migration ability of prostate cancer cells.Knockdown of PGAM1 inhibits the proliferation and migration ability of prostate cancer cells.2)PGAM1 may activate the epithelial mesenchymal transition(EMT)signaling pathway in prostate cancer cells via exosomes to promote the migration of tumor cells. |
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