Zinc oxide nanoparticle regulates the ferroptosis, proliferation, invasion and steaminess of cervical cancer by miR-506-3p/CD164 signaling

Abstract

BackgroundCancer stem cell (CSC) and ferroptosis play critical roles in cancer development, but the underlying mechanisms remain unclear. Cervical cancer induces a great mortality and an increased incidence globally. Zinc oxide nanoparticle is the nanomaterial that has been applied in industrial products and targets multiple cancer cell types and cancer stem cells. Here, we aimed to explore the effect of ZON on CSC and ferroptosis of cervical cancer.MethodsIn the present study, we identified that the treatment of ZON in vitro inhibited the proliferation of cervical cancer cells.ResultsThe ZON stimulated the apoptosis of cervical cancer cells. The tumor growth of cervical cancer cells was attenuated by ZON in the xenograft mouse model in vivo. Meanwhile, ZON represses cell invasion and migration of cervical cancer. Crucially, the sphere formation numbers were repressed by ZON. Meanwhile, the SP ratio of cervical cancer cells was inhibited by ZON. The expression of CSC markers, including Sox-2, Oct3/4, and Nanog, was suppressed by circFoxo3 inhibition. Moreover, the ferroptosis was enhanced by ZON in cervical cancer cells. About the mechanism, we observed that ZON enhanced miR-506-3p expression and CD164 was a target of miR-506-3p, in which ZON inhibited CD164 expression by promoting miR-506-3p in cervical cancer cells. We validated that CD164 reversed miR-506-3p-mediated stemness and ferroptosis in cervical cancer cells. ZON repressed stemness and reduced ferroptosis of cervical cancer cells by targeting CD164. ZON inhibits cell growth of cervical cancer in vivo by targeting CD164.ConclusionsIn brief, we concluded that ZON regulated the ferroptosis, proliferation, invasion, and steaminess of cervical cancer by miR-506-3p/CD164 signaling. Our finding provides new insights into the mechanism by which ZON regulates ferroptosis and steaminess of cervical cancer by a miR-506-3p/CD164 axis.