ALYREF enhances breast cancer progression by regulating EZH2

Breast cancer is one of the most common malignant tumors in women worldwide. Similarly, Canine mammary tumors (CMTs) are mostly diagnosed as spontaneous diseases in female dogs. Many studies have suggested that CMTs serve as good models for human breast cancer. However, comparative approaches to histone modifications are still lacking. This study aimed to compare the canine mammary tumor Histone H3 lysine 4 trimethylation (H3K4me3) landscape with that in human breast cancer. Our H3K4me3 ChIP-seq data from CMTs revealed a significant enrichment of H3K4me3 in the ALYREF gene promoter in tumor tissues compared to normal tissues. Furthermore, our study and publicly available RNA-sequencing data revealed that ALYREF expression was elevated in malignant tissues and breast cancer cell lines, and its upregulation was associated with poor prognosis in humans. Depletion of ALYREF resulted in changes in cellular phenotypes, including increased proliferation and colony formation, as well as decreased apoptosis. ALYREF increased cell viability and anchorage-independent growth while decreasing apoptosis by regulating the mRNA expression and protein levels of enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), which promotes hormone receptor-positive breast cancer and CMTs via epigenetic modifications. This suggests that ALYREF may function as a contributing factor to malignant transformation in both CMT and human breast cancer.