biostudies-literatureUnknown12(7)He J<h4>Background</h4>Lung cancer is a common malignant tumor with high morbidity and mortality rate. Glucosamine 6-phosphate N-acetyltransferase (<i>GNPNAT1</i>), which serves as a critical enzyme in hexosamine biosynthetic pathway (HBP), has been identified as a metastasis-associated gene and is upregulated in lung adenocarcinoma (LUAD). However, the exact role and related mechanism of <i>GNPNAT1</i> in LUAD metastasis remain unknown.<h4>Methods</h4>We analyzed the expression of <i>GNPNAT1</i> in the public databases and confirmed the results by immunohistochemistry (IHC). The biological functions of <i>GNPNAT1</i> in LUAD were investigated based on The Cancer Genome Atlas (TCGA). Correlations between <i>GNPNAT1</i> and cancer immune characteristics were analyzed via the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) and Cell-type Identification by Estimating Relative Subsets of RNA Transcript (CIBERSORT) R package. The underlying mechanisms of altered <i>GNPNAT1</i> expression on LUAD cell tumorigenesis, proliferation, migration, invasion, and metastasis were explored in vitro and in vivo.<h4>Results</h4>We demonstrated that <i>GNPNAT1</i> expression was significantly increased in LUAD and negatively associated with the overall survival (OS) of patients. <i>hsa-miR-1-3p</i> and <i>hsa-miR-26a-5p</i> were identified as upstream miRNA targets of <i>GNPNAT1</i>. <i>GNPNAT1</i> was associated with the infiltration levels of CD8 T cells, memory-activated CD4 T cells, NK cells resting, macrophages M0, macrophages M1, neutrophils, gamma delta T cells, and eosinophils, while it was negatively correlated with memory-resting CD4 T cells, regulatory T cells (Tregs), resting NK cells, monocytes, resting dendritic cells, and resting mast cells. <i>GNPNAT1</i> knockdown significantly inhibited proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) process, and metastasis of LUAD cells, while overexpression of <i>GNPNAT1</i> revealed the opposite effects. Rescue assay showed that <i>Snai2</i> knockdown reversed <i>GNPNAT1</i>-induced LUAD cells migration, invasion, and EMT. Mechanistically, <i>GNPNAT1</i> promoted cancer cell metastasis via repressing ubiquitination degradation of <i>Snai2</i> in LUAD.<h4>Conclusions</h4>Taken together, these data indicate that <i>GNPNAT1</i> serves as a prognostic biomarker for LUAD patient. Additionally, <i>GNPNAT1</i> is critical for promoting tumorigenesis and metastasis of LUAD cells and may be a potential therapeutic target for preventing LUAD metastasis.Biomedicines1477https://www.ebi.ac.uk/biostudies/studies/S-EPMC11274686biostudies-literatureGNPNAT1 Serves as a Prognostic Biomarker Correlated with Immune Infiltration and Promotes Cancer Cell Metastasis through Stabilization of Snai2 in Lung Adenocarcinoma.PMC11274686Ren XJing ZHe JJia DLi FZeng YYu YfalseGNPNAT1 Serves as a Prognostic Biomarker Correlated with Immune Infiltration and Promotes Cancer Cell Metastasis through Stabilization of Snai2 in Lung Adenocarcinoma.<h4>Background</h4>Lung cancer is a common malignant tumor with high morbidity and mortality rate. Glucosamine 6-phosphate N-acetyltransferase (<i>GNPNAT1</i>), which serves as a critical enzyme in hexosamine biosynthetic pathway (HBP), has been identified as a metastasis-associated gene and is upregulated in lung adenocarcinoma (LUAD). However, the exact role and related mechanism of <i>GNPNAT1</i> in LUAD metastasis remain unknown.<h4>Methods</h4>We analyzed the expression of <i>GNPNAT1</i> in the public databases and confirmed the results by immunohistochemistry (IHC). The biological functions of <i>GNPNAT1</i> in LUAD were investigated based on The Cancer Genome Atlas (TCGA). Correlations between <i>GNPNAT1</i> and cancer immune characteristics were analyzed via the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) and Cell-type Identification by Estimating Relative Subsets of RNA Transcript (CIBERSORT) R package. The underlying mechanisms of altered <i>GNPNAT1</i> expression on LUAD cell tumorigenesis, proliferation, migration, invasion, and metastasis were explored in vitro and in vivo.<h4>Results</h4>We demonstrated that <i>GNPNAT1</i> expression was significantly increased in LUAD and negatively associated with the overall survival (OS) of patients. <i>hsa-miR-1-3p</i> and <i>hsa-miR-26a-5p</i> were identified as upstream miRNA targets of <i>GNPNAT1</i>. <i>GNPNAT1</i> was associated with the infiltration levels of CD8 T cells, memory-activated CD4 T cells, NK cells resting, macrophages M0, macrophages M1, neutrophils, gamma delta T cells, and eosinophils, while it was negatively correlated with memory-resting CD4 T cells, regulatory T cells (Tregs), resting NK cells, monocytes, resting dendritic cells, and resting mast cells. <i>GNPNAT1</i> knockdown significantly inhibited proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) process, and metastasis of LUAD cells, while overexpression of <i>GNPNAT1</i> revealed the opposite effects. Rescue assay showed that <i>Snai2</i> knockdown reversed <i>GNPNAT1</i>-induced LUAD cells migration, invasion, and EMT. Mechanistically, <i>GNPNAT1</i> promoted cancer cell metastasis via repressing ubiquitination degradation of <i>Snai2</i> in LUAD.<h4>Conclusions</h4>Taken together, these data indicate that <i>GNPNAT1</i> serves as a prognostic biomarker for LUAD patient. Additionally, <i>GNPNAT1</i> is critical for promoting tumorigenesis and metastasis of LUAD cells and may be a potential therapeutic target for preventing LUAD metastasis.2024-01-01T00:00:00Z2024 Jul2026-05-22T03:12:04.153Z2025-04-19T13:13:30.523ZS-EPMC112746863906204910.3390/biomedicines12071477