VEZF1 inhibits ovarian cancer cell ferroptosis and acts as an oncogene via the miR-545-3p/PLAG1 axis.

BACKGROUND: Ovarian cancer (OC) is a fatal carcinoma for women. This study attempts to explore the role of vascular endothelial zinc finger 1 (VEZF1) in OC cell ferroptosis, thereby finding a new target for OC treatment. METHODS: Expressions of VEZF1, miR-545-3p and PLAG1 in HOSE cell line and OC cell lines were determined by RT-qPCR and western blot analysis. After VEZF1 was silenced in cells, cell proliferation was examined, contents of ROS, MDA, Fe2+, GSH were detected, and expressions of ACSL4 and GPX4 were tested. Afterwards, the binding relation between VEZF1 and miR-545-3p and between miR-545-3p and PLAG1 were verified. Functional rescue assays were formulated to validate the role of miR-545-3p knockdown or PLAG1 overexpression in OC cell ferroptosis. RESULTS: VEZF1 was overexpressed in OC, and VEZF1 silencing reduced cell proliferation, elevated levels of ROS, MDA, Fe2+, inactivated levels of GSH and GPX4, and enhanced ACSL4 expression. Functionally, VEZF1 transcriptionally inhibited miR-545-3p, and miR-545-3p targeted and inhibited PLAG1. miR-545-3p knockdown or PLAG1 overexpression could reverse the effect of VEZF1 silencing on OC cell ferroptosis. CONCLUSION: VEZF1 was overexpressed in OC and it limited OC cell ferroptosis by transcriptionally inhibiting miR-545-3p and elevating PLAG1 expression.