HSPA5, as a ferroptosis regulator, may serve as a potential therapeutic for head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a ferroptosis sensitive tumor type with high mortality rate. However, it remains largely unknown whether ferroptosis influences the tumor cell in HNSCC.

MATERIALS AND METHODS: To investigate how ferroptosis regulators were differentially expressed between normal and tumor tissue, data related to HNSCC was downloaded from The Cancer Genome Atlas. The expression levels of key factors in HNSCC and the relationship between key factors and ferroptosis in HNSCC were conducted in vitro, and then analyzed to correlate with the differences in prognosis and survival. This was then combined with TNM staging data, and the migration effects of key factors in HNSCC were verified by scratch test and transwell test.

RESULTS: In this study, gene expression analysis and correlation studies between genes showed that HSPA5 was a potentially key associated ferroptosis regulator in HNSCC. Bioinformatics analysis showed that high expression of HSPA5 in HNSCC was positively correlated with poor prognosis and distal metastasis of HNSCC. In vitro immunohistochemistry and western blot tests confirmed that HSPA5 was highly expressed in HNSCC tissues and cell lines. In vitro inhibition of HSPA5 reduced the viability of HNSCC cells and increased ferroptosis. The results of scratch, transwell, and immunofluorescence tests showed that HSPA5 was related to the migration of HNSCC. In addition, a pan-cancer analysis showed that HSPA5 was also overexpressed in many types of cancer with poor prognoses.

CONCLUSION: In total, our study demonstrates the critical role of ferroptosis regulators in HNSCC and that HSPA5, as a ferroptosis regulator, can be regarded as a key molecular target for designing new therapeutic regimens to control HNSCC metastasis and progression.