Direct and indirect regulation of CD46 by p53. (A) p53 bound to the CD46 and TNFRSF10B genes. ChIP assays were performed in TP53^wt NCI-H929 HMCL treated (Nut) or not (Ct) for 5 hours with 10 μM nutlin3a, as described in Materials and methods. (B) p53 upregulated miRNAs predicted to target CD46. MM1S and BCN were treated with nutlin3a overnight, and miRNA expression was assessed by RT-PCR. Shared miRNAs are indicated by purple color. (C) Nutlin3a-induced miRNA upregulation was restricted to TP53^wt HMCLs. TP53^wt (BCN, XG6, and NCI-H929) and TP53^abn (KMS12PE, NAN8, OPM2, and LP1) HMCLs were treated 24 hours with nutlin3a, and miRNA expression was assessed by RT-QPCR. *P = .05. (D) miRNA192# regulated CD46 expression in TP53^wt and TP53^abn HMCLs. TP53^wt (BCN, MM1S, and XG6) and TP53^abn (LP1, OMP2, KMM1, and U266) HMCLs were transfected or not (Cont) with miRNA precursors, and CD46 expression was assessed using flow cytometry 24 hours after transfection. Statistical analyses were performed using paired Student t tests. (E) Transfection of miRNA192# precursor decreased MV infection. BCN cells were transfected or not (Cont) with miRNAs precursors and exposed to MV-GFP 24 hours after transfection. CD46 expression was assessed 24 hours after transfection, and GFP expression was assessed 2 days later. Statistical analyses were performed using paired Student t tests. *P < .05; **P < .01; ***P < .001.