# A Subset of HOX Genes Negatively Correlates with HOX/PBX Inhibitor Target Gene Expression and Is Associated with Apoptosis, DNA Repair, and Metabolism in Prostate Cancer

## TL;DR

Some HOX genes are linked to cancer growth pathways and reduced cell adhesion in prostate cancer.

## Contribution

Identifies a specific HOX gene subset correlated with cancer-related pathways and patient age in prostate cancer.

## Key findings

- A subgroup of HOX genes negatively correlates with Fos, DUSP1, and ATF3 expression in prostate cancer.
- These HOX genes correlate with DNA repair and aminoacyl tRNA biosynthesis pathways.
- The HOX gene subset shows negative correlation with cell adhesion-promoting genes.

## Abstract

Background/Objectives: The HOX genes encode a family of homeodomain-containing transcription factors that have important roles in defining cell and tissue identity in embryonic development, but which also show deregulated expression in many cancers and have been shown to have pro-oncogenic roles. Due to their functionally redundant nature, strategies to target HOX protein function in cancer have focused on their interaction with their PBX cofactor using competitive peptides such as HXR9. HOX/PBX inhibition triggers apoptosis through a sudden increase in target gene expression, including Fos, DUSP1, and ATF3, which are otherwise repressed by HOX/PBX binding. Methods: We analyzed publicly available transcriptomic data in the R2 platform. Results: We show that a specific subgroup of HOX genes is negatively correlated with Fos, DUSP1, and ATF3 expression in prostate cancer, and that this subgroup also shows a strong positive corelation with pathways that support tumour growth, most notably DNA repair and aminoacyl tRNA biosynthesis, and a negative correlation with genes that promote cell adhesion and prevent motility. In addition, this set of HOX genes strongly correlates with patient age, reflecting a previously identified progressive loss of regulation of HOX expression in normal peripheral blood cells. Conclusions: Our findings indicate these HOX genes may have pro-oncogenic functions in prostate cancer.