Abstract

Cell division cycle 20 homologue (CDC20), a key regulator of mitosis, is frequently overexpressed in cancers and linked to tumor progression. However, its role in mantle cell lymphoma (MCL) remains unclear. This study explored the functional significance of CDC20 in MCL and its underlying mechanisms. CDC20 expression was analyzed in peripheral blood mononuclear cells (PBMCs), bone marrow mononuclear cells (BMNCs), clinical samples, and MCL cell lines (Z138, Mino, Rec1), followed by correlation with clinicopathological features. MCL cells were treated with the CDC20 inhibitor apcin or transduced with CDC20-knockdown lentivirus, and effects on proliferation, apoptosis, cell cycle, migration, and invasion were assessed. The anti-tumor effect of apcin was tested in the Z138-driven xenograft mouse model. RNA-seq was performed to identify signaling pathways altered upon CDC20 inhibition, and western blot (WB) analysis confirmed the dysregulation of key pathway components. Consequently, CDC20 was significantly upregulated in PBMCs, BMNCs, tumor tissues, and MCL cell lines compared to their respective controls. Apcin or CDC20 knockdown suppressed proliferation, migration, and invasion while inducing apoptosis and G2/M arrest in MCL cells. In vivo, apcin effectively and safely inhibited tumor growth. RNA-seq revealed differential genes were enriched in the PI3K/AKT signaling pathway. WB validated reduced PI3K/AKT phosphorylation levels after CDC20 inhibition, suggesting CDC20 promoted the malignant phenotype of MCL via PI3K/AKT signaling. Therefore, CDC20 plays a critical role in MCL pathogenesis. Targeting CDC20 and the PI3K/AKT pathway may offer a promising therapeutic strategy for MCL.