Vitamin D Regulates Cooperation Between Metadherin and Transcription Factor Lymphoid Enhancer-Binding Factor 1 in Prostate Cancer Development and Progression

The incidence of prostate cancer is increasing, and its poor prognosis is associated with metadherin overexpression; however, its molecular mechanisms are unclear. This study used Western blot, quantitative real-time polymerase chain reaction, immunofluorescence, and tumorigenicity assays to investigate metadherin and epithelial-mesenchymal transition in prostate cancer. We found that metadherin was highly expressed in prostate cancer tissues, especially PC-3 cells. Metadherin overexpression promoted t epithelial-mesenchymal transition and tumor growth. Bioinformatics analysis and assays revealed that lymphoid enhancer-binding factor 1 directly activates the metadherin promoter. The epithelial-mesenchymal transition and tumorigenicity were suppressed by the silencing of lymphoid enhancer-binding factor 1; however, these effects were reversed by metadherin overexpression. Vitamin D treatment downregulated metadherin and lymphoid enhancer-binding factor 1, counteracting lymphoid enhancer-binding factor 1-induced metadherin upregulation. Our findings indicate that metadherin enhances epithelial-mesenchymal transition and tumorigenicity through lymphoid enhancer-binding factor 1, with vitamin D modulating this interaction in prostate cancer.