Designation of enzyme activity of glycine-N-acyltransferase family genes and depression of glycine-N-acyltransferase in human hepatocellular carcinoma

Matsuo, Moe; Terai, Kensuke; Kameda, Noriaki; Matsumoto, Aya; Kurokawa, Yumiko; Funase, Yuichi; Nishikawa, K.; Sugaya, Naoki; Hiruta, Nobuyuki; Kishimoto, Toshihiko

doi:10.1016/j.bbrc.2012.03.099

Cited by 41 publications

(85 citation statements)

References 16 publications

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“…GLYAT enzyme activity reaches its peak at about 18 months of age, stays at this level until approximately the age of 40, and then declines slightly in the elderly (Temellini et al, 1993;Mawal et al, 1997). It has also recently been demonstrated that GLYAT expression is transcriptionally down-regulated in hepatocellular carcinoma specimens, and that diet influences the expression of GLYAT in the livers of rats (Matsuo et al, 2012;Wen et al, 2013). In the case of the South African isovaleric acidemia patients, factors other than polymorphisms of the GLYAT SA38 S17T/N156S TK1 S17T/N156S AMR01113 S17T/N156S/P295L ASN00404 S17T/N156S AMR00637 S17T/N156S AFR19438 S17T/N36S/N156S EUR00097 S17T/N156S AFR18487 S17T/N156S gene may therefore better explain the interindividual variation in responsiveness to glycine supplementation.…”

Section: Factors That Influence Interindividual Variation In Glycine mentioning

confidence: 95%

Conservation of the coding regions of the glycine N-acyltransferase gene further suggests that glycine conjugation is an essential detoxification pathway

Sluis

Badenhorst

Erasmus

et al. 2015

Gene

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Section: Factors That Influence Interindividual Variation In Glycine mentioning

confidence: 95%

Conservation of the coding regions of the glycine N-acyltransferase gene further suggests that glycine conjugation is an essential detoxification pathway

Sluis

Badenhorst

Erasmus

et al. 2015

Gene

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“…GLYATL1 encodes an enzyme that catalyzes arylacetyl transfer . In noncancerous tissue it was found to be highly expressed in liver and kidney, and to a lesser extent in pancreas, testis, ovary and stomach .…”

Section: Introductionmentioning

confidence: 99%

“…2,3 GLYATL1 encodes an enzyme that catalyzes arylacetyl transfer. 4,5 In noncancerous tissue it was found to be highly expressed in liver and kidney, and to a lesser extent in pancreas, testis, ovary and stomach. 6 Human glycine N-acyltransferases (GLYATL, GLYATL1, GLYATL2, and GLYATL3) are involved in conjugation of carboxylic acids to glycine and glutamine.…”

Section: Introductionmentioning

confidence: 99%

Characterization of glycine‐N‐acyltransferase like 1 (GLYATL1) in prostate cancer

et al. 2019

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Background Recent microarray and sequencing studies of prostate cancer showed multiple molecular alterations during cancer progression. It is critical to evaluate these molecular changes to identify new biomarkers and targets. We performed analysis of glycine‐N‐acyltransferase like 1 (GLYATL1) expression in various stages of prostate cancer in this study and evaluated the regulation of GLYATL1 by androgen. Method We performed in silico analysis of cancer gene expression profiling and transcriptome sequencing to evaluate GLYATL1 expression in prostate cancer. Furthermore, we performed immunohistochemistry using specific GLYATL1 antibody using high‐density prostate cancer tissue microarray containing primary and metastatic prostate cancer. We also tested the regulation of GLYATL1 expression by androgen and ETS transcription factor ETV1. In addition, we performed RNA‐sequencing of GLYATL1 modulated prostate cancer cells to evaluate the gene expression and changes in molecular pathways. Results Our in silico analysis of cancer gene expression profiling and transcriptome sequencing we revealed an overexpression of GLYATL1 in primary prostate cancer. Confirming these findings by immunohistochemistry, we show that GLYATL1 is overexpressed in primary prostate cancer compared with metastatic prostate cancer and benign prostatic tissue. Low‐grade cancers had higher GLYATL1 expression compared to high‐grade prostate tumors. Our studies showed that GLYATL1 is upregulated upon androgen treatment in LNCaP prostate cancer cells which harbors ETV1 gene rearrangement. Furthermore, ETV1 knockdown in LNCaP cells showed downregulation of GLYATL1 suggesting potential regulation of GLYATL1 by ETS transcription factor ETV1. Transcriptome sequencing using the GLYATL1 knockdown prostate cancer cell lines LNCaP showed regulation of multiple metabolic pathways. Conclusions In summary, our study characterizes the expression of GLYATL1 in prostate cancer and explores the regulation of its regulation in prostate cancer showing role for androgen and ETS transcription factor ETV1. Future studies are needed to decipher the biological significance of these findings.

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“…2e). These enzymes transfer an acyl group from acyl-CoA to the N-terminus of amino acids, mainly glycine (a reaction referred to as glycine conjugation) [32][33][34] . This reaction is important for the detoxification of xenobiotics, such as benzoate, because GLYATs target not only acyl-CoA but also xenobiotic acyl-CoA, which has the potential to sequester coenzyme A (CoASH) and inhibit several enzymes 34,35 .…”

Section: Resultsmentioning

confidence: 99%

Identification of critical genetic variants associated with metabolic phenotypes of the Japanese population

et al. 2020

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We performed a metabolome genome-wide association study for the Japanese population in the prospective cohort study of Tohoku Medical Megabank. By combining whole-genome sequencing and nontarget metabolome analyses, we identified a large number of novel associations between genetic variants and plasma metabolites. Of the identified metabolite-associated genes, approximately half have already been shown to be involved in various diseases. We identified metabolite-associated genes involved in the metabolism of xenobiotics, some of which are from intestinal microorganisms, indicating that the identified genetic variants also markedly influence the interaction between the host and symbiotic bacteria. We also identified five associations that appeared to be female-specific. A number of rare variants that influence metabolite levels were also found, and combinations of common and rare variants influenced the metabolite levels more profoundly. These results support our contention that metabolic phenotyping provides important insights into how genetic and environmental factors provoke human diseases.

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Designation of enzyme activity of glycine-N-acyltransferase family genes and depression of glycine-N-acyltransferase in human hepatocellular carcinoma

Cited by 41 publications

References 16 publications

Conservation of the coding regions of the glycine N-acyltransferase gene further suggests that glycine conjugation is an essential detoxification pathway

Conservation of the coding regions of the glycine N-acyltransferase gene further suggests that glycine conjugation is an essential detoxification pathway

Characterization of glycine‐N‐acyltransferase like 1 (GLYATL1) in prostate cancer

Identification of critical genetic variants associated with metabolic phenotypes of the Japanese population

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