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.