| Background and objectiveProstate cancer(PCa)ranks second in the incidence of male cancer in the world.The incidence of prostate cancer in China has increased rapidly,and prostate cancer research has received more attention.The metabolism of prostate tumor cells is significantly different from that of other tumor cells.Therefore,it is necessary to further understand the potential mechanism of prostate tumor cell development and its metabolic reprogramming.PKC-ζ plays a role in promoting tumor progression in melanoma and breast cancer,and plays a role in inhibiting tumor progression in lung cancer and colon cancer.PKC-ζ plays a dual role in tumor progression.Whether PKC-ζ is involved in the regulation of the metabolism of prostate cancer cells and affects the production of lactic acid,which has an understanding of the effects of prostate tumor cell function,is currently insufficient.The purpose of this study was to investigate the relationship between the expression of PKC-ζ in prostate cancer and the progression of prostate cancer,and to construct the over expression of PKC-ζ for prostate cancer cell line.The prostate cancer cells with the over expression of PKC-ζ perform a full transcriptase sequencing analysis,which analyzes the changes in related pathways and analyzes its metabolic pathways.Lactic acid have an influence on the function of tumor cell growth,migration,invasion,etc.And to explore the potential mechanism that provides new ideas and new targets for prostate cancer treatment.Contents and methods1.The data analysis of TCGA indicated that the expression of PKC-ζ in prostate tumor was negatively correlated with its progression.The expression of PKC-ζ had a negative correlation with LDHA.The results of transcriptome sequencing were closely related to the amino acid metabolic pathway.1.1 The expression of PKC-ζ in TCGA prostate cancer specimens was negatively correlated with tumor progression.1.2 Successfully verified the over-expression of prostate cancer cell line PKC-ζafter screening.1.3transcriptome sequencing analysis suggested that amino acid metabolism,arginine biosynthesis pathway is related,the expression ASS1 and ASNS are down-regulated.1.4The expression of PKC-ζ in prostate cancer specimens is negatively correlated with LDHA.2.Over expression of PKC-ζ in prostate cancer cells leads to down-regulation of LDHA and MCT4,affecting the production and secretion of lactic acid,and has no obvious effect on glucose uptake and utilization,thereby inhibiting its functions of growth,migration and invasion.2.1 The knockdown effect of the siPKCζ group of prostate cancer cells was successfully verified.2.2 Down-regulation of PKC-ζ promoted the proliferation of prostate cancer cells,and increased expression of PKC-ζ inhibited the proliferation of prostate cancer cells.2.3 The over expression of PKC-ζ in prostate cancer cells inhibited lactic acid to be produced,and the lactic acid concentration in serum of patients with prostate cancer was significantly higher than that in the control group(P<0.01).2.4 The over expression of PKC-ζ in prostate cancer cells inhibited migration and invasion,and lactic acid promoted migration and invasion.(P<0.01).2.SThe effect of over-expressing PKC-ζ in prostate cancer cells on the expression of HK2 was examined,and the glucose concentration in the supernatant of the PKC-ζ group and the control group was detected.2.6 The over expression of PKC-ζ in prostate cancer cells down-regulate the expression of LDHA and MCT4,and reduce lactate secretion.Results1.By analyzing the data of TCGA,it is suggested that the expression of PKC-ζ in prostate cancer are negatively correlated with its grading and stage,and the expression of PKC-ζ are also negatively correlated with LDHA.The transcriptome sequencing results of the over expression of PKC-ζ in prostate cancer cells suggest that PKC-ζ is closely related to amino acid metabolism and arginine synthesis pathway,in which ASS1 and ASNS expression are down-regulated and Slcl6A10 is significantly up-regulated.2.The concentration of serum lactic acid in patients with prostate cancer was significantly higher than that of the control,and the over expression of PKC-ζ in prostate cancer cells inhibited the production of lactic acid,but had no significant effect on the expression of HK2 and glucose uptake in prostate cancer cells.The expression of PKC-ζ is down-regulated,the proliferative activity are increased,the expression of PKC-ζ is up-regulated,and the proliferation is inhibited.3.The over expression of PKC-ζ in prostate cancer cells inhibited invasion and migration,and increased lactic acid promoted invasion and migration of prostate cancer and reduced expression of LDHA and MCT4.Conclusion1.With the malignant progression of prostate cancer,the expression of PKC-ζ is down-regulated and the expression of LDHA is up-regulated.2.The over expression of PKC-ζ in prostate cancer cells inhibited lactic acid production,and had no significant effect on Warburg effect.The expression of PKC-ζregulated proliferation,migration and invasion,and lactic acid could promote the migration and invasion of prostate cancer.3.The potential mechanism of PKC-ζ in prostate cancer cells is that the expression of PKC-ζ is up-regulated,leading to abnormal amino acid metabolism,in which LDHA expression is down-regulated,lactic acid production is reduced,and thus prostate cancer growth,invasion and migration are inhibited. |
PDF Full Text Request