KDM2B promotes cell viability by enhancing DNA damage response in canine hemangiosarcoma

Area of Science:

• Oncology
• Epigenetics
• Canine Cancer Research

Background:

• Epigenetic regulators are crucial in tumorigenesis, but their role in canine hemangiosarcoma (HSA), an endothelial cell cancer, is understudied.
• Lysine-specific demethylase 2b (KDM2B) is a key epigenetic regulator implicated in various cancers.

Purpose of the Study:

• To investigate the role of KDM2B in canine hemangiosarcoma (HSA) pathogenesis.
• To evaluate KDM2B inhibition and histone demethylase inhibitors as potential therapeutic strategies for HSA.

Main Methods:

• KDM2B expression analysis in HSA cell lines and clinical samples.
• In vitro studies involving KDM2B silencing in HSA cells.
• In vivo studies using doxycycline-induced KDM2B silencing in tumor xenografts.
• Treatment of HSA cells and xenografts with GSK-J4, a histone demethylase inhibitor.

Main Results:

• KDM2B is highly expressed in HSA cell lines and clinical cases compared to normal canine endothelial cells.
• KDM2B silencing in vitro induced apoptosis and cell death by disrupting DNA repair pathways and increasing DNA damage.
• KDM2B silencing and GSK-J4 treatment significantly reduced tumor size in vivo.
• GSK-J4 treatment induced apoptosis and cell death in HSA cells.

Conclusions:

• KDM2B functions as an oncogene in HSA by enhancing the DNA damage response.
• Pharmacological inhibition of KDM2B, specifically using GSK-J4, demonstrates therapeutic potential for HSA treatment.
• GSK-J4 represents a promising alternative therapeutic agent for HSA, potentially comparable to doxorubicin.