Zhou WB, et al. - Dysregulation of tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin ligase, contributes to the progression of human malignancies, so researchers investigated its clinical significance in breast cancer using in vitro and in vivo models. They assessed its expression by quantitative real-time PCR, Western blot, and immunohistochemistry. Luciferase reporter assay was used to investigate the upstream regulation of TRIM21. Findings revealed a decreased TRIM21 expression in breast cancer tissues at the mRNA and protein levels vs expression in nontumorous tissues. They identified a close correlation of TRIM21 expression with tumor size, estrogen receptor, human epidermal growth factor receptor 2, and clinical stage. Two independent cohorts containing 1,219 patients with breast cancer showed poor overall and disease-free survival in correlation with low TRIM21 expression. Findings thus suggest the possible utility of TRIM21 as a predictive biomarker, and that it acts as a tumor suppressor in breast cancer.