Expression of sarcosine-metabolizing enzymes in thyroid cancer
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY
Authors: Kim, Hye Min; Lee, Yu Kyung; Koo, Ja Seung
Abstract
The purpose of this study was to investigate the expression of sarcosine metabolism-related proteins according to thyroid cancer subtypes and the implications of these findings. We performed tissue microarrays of 557 thyroid cancer cases (papillary thyroid carcinoma [PTC]: 344, follicular carcinoma [FC]: 112, medullary carcinoma [MC]: 70, poorly differentiated carcinoma [PDC]: 23, and anaplastic carcinoma [AC]: 8) and 152 follicular adenoma cases. Immunohistochemical staining for sarcosine metabolism-related molecules [glycine N-methyltransferase (GNMT), sarcosine dehydrogenase (SARDH), and l-pipecolic acid oxidase (PIPOX)] was conducted, and the results were analyzed based on clinicopathologic parameters. Results: The expression of SARDH and PIPOX was different depending on thyroid cancer subtypes. PTC showed higher expression than other subtypes (P<0.001). Among PTC, follicular variant (FV) showed lower expression than conventional type (P = 0.010 and P<0.001) and PTC with BRAF V600E mutation showed higher expression than PTC without BRAF V600E mutation (P<0.001). In univariate analysis, PIPOX positivity was associated with shorter overall survival (OS) in PTC (P = 0.024). In conclusion, the expression of sarcosine metabolism-related proteins varied according to thyroid cancer subtypes. SARDH and PIPOX showed higher expression in PTC; among PTC, FVPTC showed lower expression and PTC with BRAF V600E mutation showed higher expression.
Effect of sarcosine dehydrogenase knockdown on sarcosine metabolism-related genes expression
MENDELNET 2019: PROCEEDINGS OF 26TH INTERNATIONAL PHD STUDENTS CONFERENCE
Authors: Subrtova, Hana; Splichal, Zbynek
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.