Coxsackievirus B3 Inhibited Colorectal Cancer by Upregulating miR-214-3P and Promoting Ferroptosis.

IntroductionColorectal cancer (CRC) is the third most common cancer worldwide and a significant public health threat with far-reaching societal implications. The currently available CRC therapeutic strategies have limitations, thus requiring the development of new strategies. Coxsackievirus B3 (CVB3) exhibits strong oncolytic activity in CRC, although its mechanism of action remains unclear. This study aimed to investigate whether the induction of ferroptosis is a promising treatment strategy for CRC and whether CVB3 could activate ferroptosis during infection.MethodsIn vitro and in vivo experiments were conducted to evaluate whether CVB3 infection activates the ferroptosis pathway by upregulating miR-214-3p to suppress glutathione peroxidase 4 (GPX4) expression. Dual-luciferase assays and rescue experiments were performed to confirm this regulatory mechanism. Clinical CRC tissues and colon cancer xenograft models were used to demonstrate the mediating role of the miR-214-3p/GPX4 axis in the interaction between viral replication and ferroptosis.ResultsCVB3 demonstrated oncolytic virus properties by selectively lysing tumor cells. The in vitro and in vivo experiments confirmed that CVB3 activates the ferroptosis pathway by upregulating miR-214-3p to suppress GPX4 expression, thereby promoting viral replication and tumor regression. Antagonizing miR-214-3p reversed this process.ConclusionmiR-214-3p expression was upregulated during CVB3 infection of CRC tissues and cells, activating the ferroptosis pathway and promoting tumor cell death.