E2F1-Driven WDHD1 Transcription Enhances Cell-Cycle Progression and Promotes Pancreatic Cancer Progression.

has been identified as a crucial oncogene in various tumors, but its role in pancreatic cancer remains unexplored. This study investigated the mechanisms by which WDHD1 contributes to pancreatic cancer progression. Differential analysis of the Cancer Genome Atlas (TCGA) pancreatic cancer samples identified abnormally expressed genes. Cellular assays, including cell proliferation, flow cytometry, and apoptosis assays, demonstrated WDHD1's oncogenic role. WDHD1 expression was significantly elevated in pancreatic cancer cells and tissues compared to normal counterparts. Knockdown of WDHD1 inhibited cell proliferation, induced apoptosis, and caused G1-phase cell-cycle arrest. xenograft models further validated that WDHD1 knockdown suppressed the growth of pancreatic cancer cells. Mechanistically, WDHD1 knockdown resulted in significant reductions in CDK4 and cyclin D1 protein levels, whereas WDHD1 overexpression produced the opposite effects. Additionally, E2F1 overexpression increased the expression of at both mRNA and protein levels. Rescue experiments revealed that WDHD1 knockdown could reverse the E2F1-induced upregulation of CDK4 and cyclin D1 protein levels. In conclusion, E2F1 promotes pancreatic cancer cell proliferation and cell-cycle progression by upregulating WDHD1, which in turn enhances the expression of the CDK4-cyclin D1 complex.