Single-cell transcriptomics and metabolomics reveal the potential role of ASRGL1 in metabolic reprogramming and invasion of nasopharyngeal carcinoma cells

Abstract

Nasopharyngeal carcinoma (NPC) is an aggressive and highly metastatic malignancy, presenting significant challenges for early diagnosis and treatment. Asparaginase-like protein 1 (ASRGL1) is an important enzyme involved in amino acid metabolism, and previous studies have linked it to the progression of various tumors. However, the specific role of ASRGL1 in NPC remains unclear. This study analyzed multiple publicly available datasets related to NPC. We conducted single-cell RNA sequencing (scRNA-seq) analysis on the GSE150430 dataset to identify different cell subpopulations and examine ASRGL1 expression and its functional implications. The expression of ASRGL1 and its correlation with EMT were validated using transcriptomic data. The expression of ASRGL1 in C666–1 cells was interfered with by siRNA, cell proliferation and invasion were detected by CCK8, EdU, plate cloning, Transwell and scratch method, and EMT was evaluated by detecting the expression of E-cadherin and N-cadherin. Amino acid metabolomics and GC-MS headspace metabolomics were used to analyze the effects of ASRGL1 knockdown on the metabolic pattern of NPC cells. This study found that ASRGL1 was mainly expressed in fibroblasts, epithelial cells and myeloid cells in nasopharyngeal carcinoma (NPC). The ASRGL1-cell gene was significantly enriched in the epithelial-mesenchymal transition pathway. Knocking down ASRGL1 can further inhibit the proliferation, invasion and EMT of C666–1 cells. At the same time, the utilization of various amino acids was significantly reduced, and further GC-MS metabolomics analysis showed that the cell metabolism was unbalanced. This study elucidates the expression characteristics and potential functional roles of asparaginase-like protein 1 (ASRGL1) in nasopharyngeal carcinoma (NPC), providing new insights into its potential as a diagnostic marker and therapeutic target.