SLC3A2 identified as a new therapeutic target for head and neck squamous cell carcinoma

Abstract

The head and neck squamous cell carcinomas (HNSCC), which is the most common malignant tumor of head and neck region. Programmed cell death pathways, including the ferroptosis pathway and the disulphide cell apoptotic pathway, have received increasing amounts of attention as potential targets for cancer therapy. However, the features of genes related to disulfidptosis and ferroptosis in HNSCC remain to be investigated. We used a random survival forest (RSF) algorithm model, prognostic and immunological effects to screen SLC3A2. Drug sensitivity prediction and single-cell RNA-seq data further confirmed SLC3A2 as a therapeutic target. In addition, we validated SLC3A2 as a therapeutic target for HNSCC through in vitro experiments. In this study, we used TCGA and GEO database from multiple HNSCC cohorts to identify genes associated with disulphide-related cell death. The prognostic and immunological roles of these genes were investigated, and the key gene related to disulfidoptosis and ferroptosis, SLC3A2, was screened. Drug sensitivity prediction and single-cell RNA-seq data both indicate that SLC3A2 is a potential therapeutic target for the treatment of HNSCC. Furthermore, our experiments suggest that overexpression of SLC3A2 in the absence of glucose suppress growth of HNSCC. We also found that knock down SLC3A2 could induce growth defects. In addition, we treated cells with a RING1B inhibitor to regulate SLC3A2 mRNA expression, identifying it as a potential therapeutic target in HNSCC. These findings suggested that SLC3A2 is a critical target in HNSCC development, providing new targets and research ideas for the treatment of HNSCC.