TIMD4 exhibits regulatory capability on the proliferation and apoptosis of diffuse large B-cell lymphoma cells via the Wnt/ß-catenin pathway.

ABSTRACT

BACKGROUND: Prior studies have noted the importance of T cell immunoglobulin and mucin domain containing 4 (TIMD4) in various diseases and its functions on cell malignant behaviors. However, the biological function of TIMD4 in diffuse large B-cell lymphoma (DLBCL) is unknown. METHODS: Relative expression of TIMD4 was analyzed based on the GSE56315 array including 88 cases of human tissues. TIMD4 expression in cells was detected using a quantitative reverse transcriptase-polymerase chain reaction and western blot experiments. Cell proliferation was measured using the cell counting kit-8 (CCK-8) assay and apoptotic properties were assessed through the detection of related proteins by western blotting. The underlying molecular mechanism of TIMD4 in DLBCL was predicted and confirmed using KEGG enrichment analysis and western blotting. RESULTS: The results indicate that TIMD4 is overexpressed in DLBCL tissues and the poor prognosis of DLBCL patients is significantly linked with the higher TIMD4 expression. The loss-of-TIMD4 experiment in CYP6D reveals that knockdown of TIMD4 blocks cell growth and accelerates cell apoptosis, whereas the gain-of-TIMD4 experiment in Raji cells suggests that up-regulation of TIMD4 promotes cell proliferation and inhibits cell apoptosis. The activity of the Wnt/ß-catenin pathway is mediated by the TIMD4 expression in DLBCL cells. CONCLUSIONS: These findings demonstrate that TIMD4 is up-regulated in patients with DLBCL and the regulatory effects of TIMD4 on cell proliferation and apoptosis are associated with the Wnt/ß-catenin pathway, posing a novel target for DLBCL therapy.