E2F3 is a transcription factor that functions as a cell cycle regulator and oncogene. E2F3 binds DNA cooperatively with DP proteins at E2 recognition sites (5'-TTTC[CG]CGC-3') to regulate genes involved in cell cycle progression and DNA replication, particularly controlling the G1/S phase transition 1. E2F3 binds specifically to retinoblastoma protein (RB1) in a cell-cycle dependent manner and works with RB to coregulate spliceosomal genes 2. E2F3 is oncogenic and overexpressed across multiple cancers. In melanoma, E2F3 shows frequent copy number amplification positively correlated with expression and poor prognosis; knockdown reduces proliferation and increases G0/G1 arrest 3. E2F3 expression is reciprocally regulated by microRNAs through both post-transcriptional inhibition and negative feedback loops where E2F3 transcriptionally regulates miRNAs 4. E2F3 can be repressed by the Nanos/Pumilio complex cooperating with miRNAs 5, and by the NORAD/PUMILIO/E2F3 axis during cellular senescence 6. E2F3 promotes cancer growth by driving proliferation, regulating apoptosis, mediating metastasis, and conferring drug resistance across multiple cancer types including melanoma, oral cancer, renal cell carcinoma, and osteosarcoma 17. These multifaceted roles establish E2F3 as a significant therapeutic target in human malignancies.