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

Abstract

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.

Identification of Ten Core Hub Genes as Potential Biomarkers and Treatment Target for Hepatoblastoma

“…GLYATL1 encodes an enzyme with phenylacetyl-CoA glutamine N-acyltransferase activity, which regulates mitochondrial ATP production, glycine availability, CoASH availability, and the detoxification of various organic acids ( 50 ). In a previous study, the expression of GLYATL1 was higher in localized prostate cancers than in benign prostatic tissue and metastatic prostate cancer ( 49 , 51 ). This study also demonstrated that GLYATL1 may be associated with the grade of prostate cancer since the expression of GLYATL1 was significantly high in low-grade tumors.…”

“…These findings suggest that FANCI has a novel oncogenic role and may be useful as a prognostic biomarker and/or therapeutic target for different tumors. GLYATL1 belongs to the glycine-N-acyltransferase gene family and is normally expressed in the liver and kidney ( 49 ). GLYATL1 encodes an enzyme with phenylacetyl-CoA glutamine N-acyltransferase activity, which regulates mitochondrial ATP production, glycine availability, CoASH availability, and the detoxification of various organic acids ( 50 ).…”

Identification of potential core genes in hepatoblastoma via bioinformatics analysis

“…Enriched genes such as SULT1A2 [Fernandez-Santander et al 2013], PIK3C2G [Li et al 2015], AGL (amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase) [Richmond et al 2018], UGT2B10 [Lu et al 2018], CTH (cystathionine gamma-lyase) [Xu et al 2020] and CYP26A1 [Osanai and Lee, 2015] were involved in metabolic activity of various cancer types, but these genes may liable for metabolic activity of in hepatoblastoma. Enriched genes such as TDO2 [Pham et al 2018], EPHX2 [Vainio et al 2011], PLA2G2A [Ganesan et al 2008], INPP1 [Li et al 2019], GCH1 [Gao et al 2016], GNE (glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase) [Kemmner et al 2012], PAPSS2 [Zhang et al 2019], GLYATL1 [Eich et al 2019], CFB (complement factor B) [Kim et al 2019], C1R [Riihilä et al 2020], C1S [Riihilä et al 2020], C9 [Chong et al 2010], FGB (fibrinogen beta chain) [Repetto et al 2018] and KNG1 [Quesada-Calvo et al 2017] were linked with development of various cancer types, but these genes may be culpable for advancement of hepatoblastoma. Methylation inactivation of tumor suppressor enriched genes such as HAAO (3-hydroxyanthranilate 3,4-dioxygenase) [Huang et al 2010] and AOX1 [Vantaku et al 2019] were identified with growth of various cancer types, but loss of these genes may be liable for progression of hepatoblastoma.…”

The expression and prognostic value of GLYATL1 and its potential role in hepatocellular carcinoma

“…GLYATL1 is involved not only in normal physiological metabolism but also in tumorigenesis. A previous study demonstrated that the mRNA expression of GLYATL1 was unregulated by androgen and ETS variant transcription factor 1 (ETV1) in prostate cancer (10). Moreover, Kishimoto and colleagues showed that the protein expression of GLYATL1 in HCC tissues was lower than that in non-tumor tissues (9).…”