Effect of sarcosine dehydrogenase knockdown on sarcosine metabolism-related genes expression

Abstract

Sarcosine is extensively discussed as potential prostate cancer oncometabolite. Sarcosine dehydrogenase (SARDH) is one of the key enzymes involved in sarcosine metabolism that catalyses oxidative demethylation of sarcosine to glycine in mitochondrion. This study investigates the effects of small interfering RNA (siRNA) mediated SARDH knockdown on gene expression of sarcosine metabolism related enzymes: glycine N-methyltransferase (GNMT), peroxisomal sarcosine oxidase (PIPOX) and dimethylglycine dehydrogenase (DMGDH). The effect of SARDH knockdown was studied in three human prostate cell lines (PNT1A, DU-145, PC3) and gene expression was evaluated by quantitative real-time PCR (qPCR). Although the lowest SARDH knockdown was achieved in cancer DU-145 cell line, the highest changes in expression of other sarcosine metabolism genes were detected. In particular, the significant increase in DMGDH and PIPOX expression was observed. Our findings revealed potential stimulation effect of SARDH knockdown on DMGDH and PIPOX expression in prostate cancer cell line DU-145.Sarcosine is extensively discussed as potential prostate cancer oncometabolite. Sarcosine dehydrogenase (SARDH) is one of the key enzymes involved in sarcosine metabolism that catalyses oxidative demethylation of sarcosine to glycine in mitochondrion. This study investigates the effects of small interfering RNA (siRNA) mediated SARDH knockdown on gene expression of sarcosine metabolism related enzymes: glycine N-methyltransferase (GNMT), peroxisomal sarcosine oxidase (PIPOX) and dimethylglycine dehydrogenase (DMGDH). The effect of SARDH knockdown was studied in three human prostate cell lines (PNT1A, DU-145, PC3) and gene expression was evaluated by quantitative real-time PCR (qPCR). Although the lowest SARDH knockdown was achieved in cancer DU-145 cell line, the highest changes in expression of other sarcosine metabolism genes were detected. In particular, the significant increase in DMGDH and PIPOX expression was observed. Our findings revealed potential stimulation effect of SARDH knockdown on DMGDH and PIPOX expression in prostate cancer cell line DU-145.