PI3K-regulated Glycine N-methyltransferase is required for the development of prostate cancer

Zabala-Letona, Amaia; Arruabarrena-Aristorena, Amaia; Fernández-Ruiz, Sonia; Viera, Cristina; Carlevaris, Onintza; Ercilla, Amaia; Mendizabal, Isabel; Martín, T.; Macchia, Alice; Camacho, Laura; Pujana-Vaquerizo, Mikel; Sánchez-Mosquera, Pilar; Torrano, Verónica; Martín-Martín, Natalia; Zúñiga-García, Patricia; Castillo-Martin, Mireia; Ugalde-Olano, Aitziber; Loizaga-Iriarte, Ana; Unda, Miguel; Mato, José M.; Berra, Edurne; Martínez‐Chantar, María Luz; Carracedo, Arkaitz

doi:10.1038/s41389-022-00382-x

“…SAM is an important methyl donor in various biological processes, including the methylation of DNA and histones, which can affect gene expression [ 70 ]. Gnmt is involved in the catabolism of SAM, regulating SAM levels in the brain [ 71 ]. Decreased Gnmt expression has been observed with age and neurodegenerative diseases [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide Mononucleotide (NMN) Works in Type 2 Diabetes through Unexpected Effects in Adipose Tissue, Not by Mitochondrial Biogenesis

Popescu,

Dinischiotu,

Soare

et al. 2024

IJMS

0

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Nicotinamide mononucleotide (NMN) has emerged as a promising therapeutic intervention for age-related disorders, including type 2 diabetes. In this study, we confirmed the previously observed effects of NMN treatment on glucose uptake and investigated its underlying mechanisms in various tissues and cell lines. Through the most comprehensive proteomic analysis to date, we discovered a series of novel organ-specific effects responsible for glucose uptake as measured by the IPGTT: adipose tissue growing (suggested by increased protein synthesis and degradation and mTOR proliferation signaling upregulation). Notably, we observed the upregulation of thermogenic UCP1, promoting enhanced glucose conversion to heat in intermuscular adipose tissue while showing a surprising repressive effect on mitochondrial biogenesis in muscle and the brain. Additionally, liver and muscle cells displayed a unique response, characterized by spliceosome downregulation and concurrent upregulation of chaperones, proteasomes, and ribosomes, leading to mildly impaired and energy-inefficient protein synthesis machinery. Furthermore, our findings revealed remarkable metabolic rewiring in the brain. This involved increased production of ketone bodies, downregulation of mitochondrial OXPHOS and TCA cycle components, as well as the induction of well-known fasting-associated effects. Collectively, our data elucidate the multifaceted nature of NMN action, highlighting its organ-specific effects and their role in improving glucose uptake. These findings deepen our understanding of NMN’s therapeutic potential and pave the way for novel strategies in managing metabolic disorders.

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“…The sarcosine has showed an oncogenic potential in prostate cancer and promotes cancer cell invasion. Knockdown of SARDH induces an invasive phenotype in benign prostate epithelial cells [39][40][41]. In examination of urine samples collected from patients with HCC, GNMT was identified as a biomarker associated with HCC prognosis, and there was a strong correlation between sarcosine and GNMT [42].…”

Section: Discussionmentioning

confidence: 99%

Sarcosine dehydrogenase as an immune infiltration-associated biomarker for the prognosis of hepatocellular carcinoma

Xie,

Yang,

Qin

et al. 2024

J. Cancer

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This study was aimed to investigate the prognostic value and clinical significance of sarcosine dehydrogenase (SARDH) in hepatocellular carcinoma (HCC) and to explore the underlying mechanisms. The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), HPA and CPTAC databases were adopted to analyze the expression of SARDH mRNA and protein between normal liver tissue and HCC, and examine their relationship with clinicopathological features. Kaplan-Meier analysis, Cox regression, as well as nomogram were adopted to explore the prognostic value of SARDH in HCC. Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia (KEGG) together with Gene Set Enrichment Analysis (GSEA) were adopted to analyze the molecular mechanisms and biological functions of SARDH in HCC; while MethSurv, STRING, GeneMANIA, TIMER database data and single-sample gene set enrichment analysis (ssGSEA) algorithm were used for other bioinformatic analysis. Furthermore, immunohistochemistry was used to verify the expression of SARDH. Compared to normal liver tissue, SARDH expression was markedly lower in HCC. A lower SARDH expression was linked with Pathologic T stage (T3&T4), pathologic stage (Stage III&IV), and histologic grade (G3&4), which further indicates worse prognosis. Besides, results of bioinformatic analysis proved that SARDH expression was correlated with immune infiltration. In addition, SARDH hypermethylation was related to a poorer prognosis. SARDH expression was related to several key genes in the Ferroptosis pathway.

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“…The sarcosine has showed an oncogenic potential in prostate cancer and promotes cancer cell invasion. Knockdown of SARDH induces an invasive phenotype in benign prostate epithelial cells (39)(40)(41). In examination of urine samples collected from patients with HCC, GNMT was identi ed as a biomarker associated with HCC prognosis, and there was a strong correlation between sarcosine and GNMT (42).…”

Section: Discussionmentioning

confidence: 99%

Sarcosine dehydrogenase as an immune infiltration-associated biomarker for the prognosis of hepatocellular carcinoma

Xie,

YANG,

QIN

et al. 2023

Preprint

0

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This study was aimed to investigate the prognostic value and clinical significance of sarcosine dehydrogenase (SARDH) in hepatocellular carcinoma (HCC) and to explore the underlying mechanisms. The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), HPA and CPTAC databases were adopted to analyze the expression of SARDH mRNA and protein between normal liver tissue and HCC, and examine their relationship with clinicopathological features. Kaplan-Meier analysis, Cox regression, as well as nomogram were adopted to explore the prognostic value of SARDH in HCC. Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia (KEGG) together with Gene Set Enrichment Analysis (GSEA) were adopted to analyze the molecular mechanisms and biological functions of SARDH in HCC; while MethSurv, STRING, GeneMANIA, TIMER database data and single-sample gene set enrichment analysis (ssGSEA) algorithm were used for other bioinformatic analysis. Furthermore, immunohistochemistry was used to verify the expression of SARDH. Compared to normal liver tissue, SARDH expression was markedly lower in HCC. A lower SARDH expression was linked with Pathologic T stage (T3&T4), pathologic stage (Stage III&IV), and histologic grade (G3&4), which further indicates worse prognosis. Besides, results of bioinformatic analysis proved that SARDH expression was correlated with immune infiltration. In addition, SARDH hypermethylation was related to a poorer prognosis. SARDH expression was related to several key genes in the Ferroptosis pathway.

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PI3K-regulated Glycine N-methyltransferase is required for the development of prostate cancer

Cited by 11 publications

References 53 publications

Nicotinamide Mononucleotide (NMN) Works in Type 2 Diabetes through Unexpected Effects in Adipose Tissue, Not by Mitochondrial Biogenesis

Nicotinamide Mononucleotide (NMN) Works in Type 2 Diabetes through Unexpected Effects in Adipose Tissue, Not by Mitochondrial Biogenesis

Sarcosine dehydrogenase as an immune infiltration-associated biomarker for the prognosis of hepatocellular carcinoma

Sarcosine dehydrogenase as an immune infiltration-associated biomarker for the prognosis of hepatocellular carcinoma

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