Down-regulation Of NFATc1 Suppresses The Proliferation,Migration,Invasion And Warburg Effect In Prostate Cancer Cells

Background Prostate cancer(PCa),accounting for 28%of all male cancer cases,is the second leading cause of cancer-related death among men.Although initially sensitive to androgen blocking therapy,prostate cancer eventually inevitably develops into androgen independent cancer with recurrence and extensive metastasis,which is the main cause of death and treatment difficulty of prostate cancer.Gene therapy has become a hot topic.It is of great significance to explore the relationship between gene functional changes and the development and malignant characteristics of prostate cancer,to reveal the precise molecular mechanism of prostate cancer metastasis,and to design reasonable gene targeted therapeutic sites.Activation of T cell nucleus factor(nuclear factor of activated T cells,NFAT)is a set of widely expressed in mammalian cells,and has the transcriptional activity of the protein,the selective induction of cytokines and other immune regulation of gene transcription,plays a central role in the process of immune response,for the first found in T cells and thus named.It is generally believed that the sequence diversity of NFAT loci and the relative position diversity of NFAT loci with other transcription factor binding sites are the basis of determining the selective gene regulation of NFAT,which is correlated with many signal pathways and can regulate the evolution,growth and differentiation of cell cycle at the transcriptional level.In addition to participating in cell cycle evolution,growth,differentiation and other regulatory functions,recent studies have also pointed out that NFAT plays a key role in cell phenotypic transformation related to tumor progression and malignancy,which is necessary for breast cancer cells,colorectal cancer cells and other cells to acquire and maintain invasiveness.NFATc1,belonging to NFAT family,is overexpressed in PCa and is correlated with the risk of recurrence after radical prostatectomy.Materials&Methods In the present study,the expression of NFATc,c-myc and PKM2 in PCa cells was regulated by lentiviruses and then detected by real-time PCR and western blot analysis.Further,the assays of proliferation,invasion and migration were performed.The glucose consumption and lactate production were assessed by biochemical detections.Results We found that NFATc1 down-regulation significantly suppressed the proliferation and Warburg effect of PCa cells,concurrent with a decrease of c-myc and PKM2 expression.Likewise,the abilities of migration and invasion were also inhibited inNFATc1-silenced PCa cells.In addition,NFATc1 down-regulation-induced inhibition of cell proliferation,migration and invasion and Warburg effect were counteracted by up-regulation of c-myc or PKM2.The expression of PKM2 was positively regulated by NFATc1 and c-myc expression.Conclusions These results indicated that NFATc1 down-regulation could suppress the proliferation,Warburg effect,and migration and invasion abilities of PCa cells,which probably by regulating c-myc and PKM2 expression.NFATc1 may be a potential therapeutic target for PCa and used as a diagnosis or prognosis indicator of PCa.