Silencing TMED2 suppresses cell growth and tumor progression in diffuse large B-cell lymphoma via inducing G0/G1 cell cycle arrest

Background Transmembrane Emp24 Domain Containing 2 (TMED2) is involved in various cancers, but its role in diffuse large B-cell lymphoma (DLBCL) remains unclear. This study investigated TMED2’s expression, biological functions, and underlying mechanisms in DLBCL. Methods TMED2 expression was analyzed in DLBCL patient samples and cell lines by qRT-PCR and Western blot (WB). Lentiviral shRNA-mediated knockdown of TMED2 was performed in SUDHL-4 and OCI-LY10 DLBCL cells. Functional impacts on proliferation, cell cycle, and apoptosis were assessed using CCK-8, flow cytometry analysis, annexin V-APC staining assays, caspase-3/7 activity assays, and WB of key regulators (cyclins, CDKs, Bax, Bcl-2, caspases). The in vivo role of TMED2 was evaluated using a subcutaneous xenograft model in nude mice. Results TMED2 expression was significantly upregulated in DLBCL tissues and cell lines. TMED2 knockdown markedly inhibited cell proliferation in vitro . This was associated with a pronounced G0/G1 phase cell cycle arrest, coupled with downregulation of key G1/S transition regulators (cyclin D1, cyclin E1, CDK2, CDK4, CDK6). Furthermore, TMED2 silencing promoted apoptosis, evidenced by increased Annexin V-positive cells, elevated caspase-3/7 activity, upregulated expression of cleaved caspase-3/caspase-7, and an increased Bax/Bcl-2 ratio. In vivo , TMED2 knockdown significantly suppressed tumor growth in xenograft models. Conclusion TMED2 promotes DLBCL progression by driving cell cycle progression and inhibiting apoptosis. Silencing TMED2 induces G0/G1 arrest and enhances caspase-dependent apoptosis. These findings identify TMED2 as a potential prognostic biomarker and therapeutic target in DLBCL.