GNPNAT1 Serves as a Prognostic Biomarker Correlated with Immune Infiltration and Promotes Cancer Cell Metastasis through Stabilization of Snai2 in Lung Adenocarcinoma.

BACKGROUND

Lung cancer is a common malignant tumor with high morbidity and mortality rate. Glucosamine 6-phosphate N-acetyltransferase (), 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 in LUAD metastasis remain unknown.

METHODS

We analyzed the expression of in the public databases and confirmed the results by immunohistochemistry (IHC). The biological functions of in LUAD were investigated based on The Cancer Genome Atlas (TCGA). Correlations between 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 expression on LUAD cell tumorigenesis, proliferation, migration, invasion, and metastasis were explored in vitro and in vivo.

RESULTS

We demonstrated that expression was significantly increased in LUAD and negatively associated with the overall survival (OS) of patients. and were identified as upstream miRNA targets of . 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. knockdown significantly inhibited proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) process, and metastasis of LUAD cells, while overexpression of revealed the opposite effects. Rescue assay showed that knockdown reversed -induced LUAD cells migration, invasion, and EMT. Mechanistically, promoted cancer cell metastasis via repressing ubiquitination degradation of in LUAD.

CONCLUSIONS

Taken together, these data indicate that serves as a prognostic biomarker for LUAD patient. Additionally, is critical for promoting tumorigenesis and metastasis of LUAD cells and may be a potential therapeutic target for preventing LUAD metastasis.