Enhancer of zeste 2 polycomb repressive complex 2 subunit overexpression suppresses apoptosis in canine T-cell lymphoma: an in vitro functional analysis

Lymphoma is one of the most common neoplastic diseases in dogs, and T-cell lymphoma in particular has frequently been reported to show limited sensitivity to conventional chemotherapy from the onset of treatment when compared with B-cell lymphoma. Owing to its high-grade and aggressive clinical behavior, there is a strong need to explore novel therapeutic approaches for canine T-cell lymphoma, including strategies targeting aberrant gene regulation. In this study, we focused on the epigenetic enzyme enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and investigated its functional role in canine T-cell lymphoma. The EZH2 gene was ectopically introduced into canine T-cell lymphoma cell lines using a lentiviral vector system, and colony-forming ability, and apoptosis rate were evaluated. EZH2 overexpression significantly enhanced colony-forming capacity, suppressed apoptosis, and increased the number of viable cells compared with control cells. These findings indicate that elevated EZH2 expression confers a survival advantage to canine T-cell lymphoma cells. The present study provides novel evidence that overexpression of EZH2 itself promotes tumor cell survival and aggressiveness. Our results suggest that EZH2 may play a functional role in the maintenance and progression of at least a subset of canine T-cell lymphoma and may represent a potential driver of tumor malignancy. These findings contribute to a deeper understanding of lymphomagenesis and support the potential of EZH2 as a therapeutic target in canine T-cell lymphoma.