# IPO9 Promotes Ovarian Cancer Progression by Suppressing HMOX1‐Dependent Ferroptosis

## TL;DR

This study identifies IPO9 as a gene that promotes ovarian cancer by blocking a type of cell death called ferroptosis, offering a new potential target for treatment.

## Contribution

The study reveals IPO9's role in suppressing HMOX1-dependent ferroptosis, a novel mechanism in ovarian cancer progression.

## Key findings

- MALAT1+ epithelial cells are linked to poor survival and immune suppression in ovarian cancer.
- IPO9 is upregulated in ovarian cancer and promotes tumor growth by inhibiting ferroptosis.
- Higher MALAT1+ cell infiltration correlates with immune dynamics and somatic mutations in OC.

## Abstract

Ovarian cancer (OC) poses a significant threat to women’s health, with current treatment strategies remaining suboptimal, necessitating the exploration of novel therapeutic targets and immune microenvironment dynamics. This study integrates multiomics data from TCGA, GEO, and IEU‐Open‐GWAS, employing scRNA‐seq, scPagwas, BayesPrism, and WGCNA to identify key cell subpopulations and genes, followed by functional validation through EdU, colony formation, Transwell assays, and ferroptosis markers (MDA, ROS, and ferrous ions). Results reveal MALAT1+ epithelial cells as a core cell subpopulation in OC, with higher abundance correlating with shorter overall survival, suppressed immune microenvironments, and potential immunotherapy resistance, while their infiltration levels are closely associated with OC immune dynamics and somatic mutations. Further analysis identifies IPO9 as a core gene upregulated in OC, promoting tumor progression by inhibiting HMOX1‐dependent ferroptosis. These findings highlight MALAT1+ epithelial cells as drivers of immune suppression in OC and propose IPO9 as a promising therapeutic target, offering new avenues for immunotherapy development.