Knockdown of TOP2A reverses cisplatin resistance in ovarian cancer by inhibiting EMT via ferroptosis mediated by the TP53/GPX4/SLC7A11 axis.

ABSTRACT:

Introduction

Cisplatin resistance is a major challenge in ovarian cancer therapy, particularly for high-grade serous ovarian cancer (HGSOC). DNA topoisomerase IIα (TOP2A) relates to cancer drug resistance, yet its role and molecular mechanisms in ovarian cancer cisplatin resistance remain unclear.

Methods

TOP2A expression was detected in HGSOC tissues and cisplatin-resistant cells (SKOV3-DDP, OVCAR3-DDP). Functional assays combined with TOP2A knockdown evaluated cisplatin sensitivity and malignant phenotypes (proliferation, invasion, migration) in resistant cells. RNA-seq and GEO cisplatin resistance dataset (GSE214302) validated TOP2A's role in cisplatin resistance, prognostic value, and associations with TP53, GPX4, SLC7A11. Molecular docking/Co-IP confirmed TOP2A-TP53 int

SUBMITTER: Liu X 

PROVIDER: S-EPMC12604993 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature