Objective To examined the role of copper starvation in oral squamous cell carcinoma (OSCC), along with the molecular functions and mechanisms of SLC31A1 in these cells.

Methods Initially, SLC31A1 was silenced to induce a copper starvation environment. Subsequently, we evaluated the effects of copper starvation on oral squamous cell carcinoma cells using the CCK-8 assay, cell scratch assay, and subcutaneous tumor formation in nude mice. In addition, changes in autophagy and EZH2 expression levels in oral squamous cell carcinoma cells were detected after SLC31A1 silencing. Lactate dehydrogenase activity was assayed to determine its impact on natural killer (NK) cell cytotoxicity after SLC31A1 silencing.

Results Silencing of SLC31A1 significantly inhibited the proliferation, migration, and subcutaneous tumor formation ability of oral squamous cell carcinoma cells. Furthermore, silencing SLC31A1 mediated EZH2 degradation and increased NK cell infiltration.

Conclusions Copper starvation can regulate the proliferation, migration, and subcutaneous tumor formation ability of oral squamous cell carcinoma and increase NK cell infiltration by modulating EZH2 expression.