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

BackgroundTransmembrane 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.MethodsTMED2 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.ResultsTMED2 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.ConclusionTMED2 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.