28 February 2019 : Laboratory Research
Down-Regulation of Nfatc1 Suppresses Proliferation, Migration, Invasion, and Warburg Effect in Prostate Cancer CellsYuanyuan Liu12A, Tao Liang2A, Xinkai Qiu1B, Xuxiao Ye2C, Zuowei Li2D, Binqiang Tian2E, Dongliang Yan2A*
Med Sci Monit 2019; 25:1572-1581
BACKGROUND: Prostate cancer (PCa), accounting for 28% of all male cancer cases, is the second leading cause of cancer-related death among men. NFATc1, belonging to the NFAT family, is overexpressed in PCa and is correlated with the risk of recurrence after radical prostatectomy.
MATERIAL AND 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, proliferation, invasion, and migration assays were performed. The glucose consumption and lactate production were assessed by biochemical detection.
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 in NFATc1-silenced PCa cells. In addition, NFATc1 down-regulation-induced inhibition of cell proliferation, migration, 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 indicate that NFATc1 down-regulation can suppress the proliferation, Warburg effect, and migration and invasion abilities of PCa cells, probably by regulating c-myc and PKM2 expression. NFATc1 may be a potential therapeutic target for PCa and could be used as a diagnosis or prognosis indicator of PCa.
Keywords: Cell Migration Inhibition, Cell Proliferation, Neoplasm Invasiveness, NFATC Transcription Factors, Prostatic Neoplasms, Carrier Proteins, Cell Movement, Down-Regulation, Gene Expression Regulation, Neoplastic, Genes, myc, Membrane Proteins, Neoplasm Recurrence, Local, Prognosis, Prostate, Thyroid Hormones, transcriptional activation
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