• Through p53-regulated gene transcription, miR-214 restoration decreased cell proliferation and triggered apoptosis in canine hemangiosarcoma cell lines.• HSA cell lines overexpressed COP1, and knocking it down caused apoptosis and upregulated p53-regulated genes.• COP1 knockdown induced apoptosis in HSA cells by up-regulating p53-regulated gene expression, similar to the results obtained using miR-214-transfection. The gene discussed is ALB; the disease is angiosarcoma.