Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the epithelial tissue of the nasopharynx. It is highly invasive and prone to regional metastasis, with a particularly high incidence in southern China and Southeast Asia (Liu et al., 2024, Su et al., 2024). Despite recent advances in radiotherapy and immunotherapy, early diagnosis and treatment of NPC remain challenging (Liu et al., 2024, Huang et al., 2023). Identifying reliable biomarkers and molecular targets for NPC is crucial for optimizing therapeutic strategies and improving patient survival.

Asparaginase-like protein 1 (ASRGL1) is an important enzyme involved in amino acid metabolism, catalyzing the hydrolysis of L-asparagine into L-aspartate and ammonia. Previous studies have demonstrated a close relationship between tumor metabolic reprogramming and the epithelial-mesenchymal transition (EMT) process, with recent research highlighting the pivotal role of amino acid metabolic reprogramming (Mao et al., 2024). Following the work of Simon et al. Knott et al. (2018), which identified asparagine's regulatory effect on EMT and metastasis in breast cancer, asparagine and asparagine synthetase (ASNS) were also found to play key roles in regulating metastasis in colorectal cancer (Du et al., 2019) and lung cancer (Cai et al., 2022). Unlike ASNS, which catalyzes the synthesis of asparagine from aspartate and glutamine, ASRGL1 regulates asparagine levels by catalyzing its hydrolysis into aspartate and ammonia.

Abnormal ASRGL1 expression has been reported in invasive ductal carcinoma of the breast and liver (Eren Karanis et al., 2021, Xue et al., 2021), suggesting that it is involved in tumorigenesis and may serve as an early diagnostic biomarker. Additionally, ASRGL1 has been shown to be closely linked to tumor growth and has been used in the treatment of acute lymphoblastic leukemia (Rigouin et al., 2017). The loss of ASRGL1 function may lead to cellular dysfunction in tumors. However, its specific role and mechanism of action in NPC remain largely unexplored. By integrating single-cell transcriptomes, cell function experiments, and cell metabolomics analysis, this study explored the expression pattern of ASRGL1 in NPC and its relationship with the invasion ability and metabolic reprogramming of NPC cells, and aimed to reveal its potential diagnostic and therapeutic significance in NPC.

In this study, We analyzed the expression distribution of ASRGL1 in nasopharyngeal carcinoma (NPC) tissues based on single-cell transcriptomic data and its association with the functions of different cell populations. By combining metabolomics and cellular function experiments after knocking down ASRGL1, we explored its impact on the invasion ability and metabolic patterns of NPC cells. This study not only reveals the potential role of ASRGL1 in NPC but also provides new insights into the regulation of amino acid metabolism, laying a theoretical foundation for the application of ASRGL1 in the diagnosis and treatment of NPC.