Introduction Expression of the immunoglobulin superfamily member CD112was increased in multiple malignancies. Importantly, its expression was observed in both PD-L1negative and positive tumors. However, the role of CD112 in tumorigenesis and tumor development in cervical cancer has not been elucidated.

Methods The expression of CD112 in cervical cancer tissues was detected using immunohistochemistry (IHC) and gene expression profiling. CCK-8, edu tests, wound healing and migration assays were used to assess the biological effects of CD112 overexpression and knockdown. Furthermore, proteomic analysis revealed the potential mechanism of CD112 in cervical cancer.

Results CD112 is expressed at high levels in cervical cancer tissues and is negatively correlated with the level of infiltrating CD8+ T cells. In addition, In vitro and in vivo, reducing the expression of CD112 inhibited cell proliferation and migration. Antibody array-based profiling of protein analysis revealed that CD112 knockdown can inhibited the SLC7A11/GPX-4 pathway and activated ferroptosis; the opposite effects were observed upon CD155 has overexpression. We further confirmed the mechanism between CD112 and SLC7A11/GPX-4pathway through rescue experiments. CD112 over-expression reversed the ferroptosis effects and inhibition of the SLC7A11/GPX-4pathway induced by GPX-4 inhibitor (rsl3).

Conclusion/Implications Our research demonstrated that CD112 can activates the SLC7A11/GPX-4 pathway and inhibit ferroptosis. Thus, CD112 is a potential screening and therapeutic biomarker for cervical cancer.